Jump to ContentJump to Main Navigation
Show Summary Details
More options …

e-Polymers

Editor-in-Chief: Agarwal, Seema


IMPACT FACTOR 2018: 1.491

CiteScore 2018: 1.31

SCImago Journal Rank (SJR) 2018: 0.311
Source Normalized Impact per Paper (SNIP) 2018: 0.432

Open Access
Online
ISSN
1618-7229
See all formats and pricing
More options …
Volume 14, Issue 6

Issues

Volume 13 (2013)

Volume 12 (2012)

Volume 11 (2011)

Volume 10 (2010)

Volume 9 (2009)

Volume 8 (2008)

Volume 7 (2007)

Volume 6 (2006)

Volume 5 (2005)

Volume 4 (2004)

Volume 3 (2003)

Volume 2 (2002)

Volume 1 (2001)

Controlled ring-opening polymerization of 1,2,6-tricyclic orthoesters of mannose toward size–controlled α-d-mannopyranan

Chanokpon Yongyat
  • School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand
  • Laboratory of Medicinal Chemistry, Chulabhorn Research Institute and Program in Chemical Biology, Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Somsak Ruchirawat
  • Laboratory of Medicinal Chemistry, Chulabhorn Research Institute and Program in Chemical Biology, Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand
  • The Center of Excellence on Environmental Health, Toxicology and Management of Chemicals, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Siwarutt Boonyarattanakalin
  • Corresponding author
  • School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-11-01 | DOI: https://doi.org/10.1515/epoly-2014-0129

Abstract

Lipomannan (LM), one of the major components of glycans found on the cell wall of Mycobacterium tuberculosis, plays a critical role in interacting with host cells and moderating immune response. The backbone of LM is composed of α(1–6) mannopyranan, consisting of approximately 10–15 repeating mannose residues. Rapid synthesis of α(1–6) mannopyranan has been accomplished by ring-opening polymerization using 3,4-O-benzyl-β-d-mannopyranose 1,2,6-orthobenzoate (1) as a starting monomer. Here, we report the progress on attempts to control the size of α(1–6) mannopyranan polymer products. It is possible to prepare α-d-mannopyranan polymer products in different sizes by varying the monomer concentration.

This article offers supplementary material which is provided at the end of the article.

Keywords: lipomannan; mannopyranan; Mycobacterium tuberculosis (Mtb); polymannoside; polymerization

1 Introduction

Tuberculosis is a leading global cause of mortality in mankind (1–3). Effective treatment of TB needs the use of large doses of coupled anti-bacterial drug combinations for a long term, which has proven to be difficult to achieve in some countries, especially in third world countries (4). The bacillus Calmette-Guérin vaccine is readily available, but has low protective efficacy and fails to protect against reactivation of pulmonary TB in adults (5, 6).

TB treatment via drug therapy is complicated by the extremely sophisticated envelope of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) (7). Furthermore, the emergence of multi-drug resistant strains and extensive-drug resistant strains of Mtb has restricted the drug therapy of TB and contributed to more epidemic concerns (8–11). Mtb has unique and complicated features that enable it to infect and survive within specific host mammalian cells. The specialized molecules that mediate host-pathogen interactions are those associated with bacterial envelopes (12). One of the interspersed molecules that comprise the biologically and physically unique envelope of Mtb is lipomannan (LM), which is composed of a linear α(1–6) mannopyranan biopolymer as its backbone (13–15). The mannopyranan backbone consists of approximately 10–15 repeating mannose residues and about half of them are further substituted with a single mannose at position 2 (14).

LMs participate in the immunomodulation of the infected hosts by inducing a significant cytokine-inducing effect. They can stimulate the mRNA expression and secretion of tumor necrosis factor-α and interleukin-8 from differentiated THP-1 cells (16). Furthermore, lipomannan is involved in the regulation of proinflammatory and anti-inflammatory cytokine production as well as apoptosis-inducing activity (17). Understanding of the interactions between LM and host immune systems will facilitate biological studies of host-pathogen interaction and lead to effective treatment and prevention of TB.

Although naturally occurring polysaccharides are available, their limited amount and the difficulty to isolate their pure state impede many of the biological studies of LM. An alternative way to access the chemically defined structure of LM is through chemical synthesis, which provides well-defined structures for detailed immunological studies (18–20).

The synthesis of LM is impossible to achieve by traditional stepwise syntheses due to its macromolecular nature. In addition to stepwise syntheses, manual and automated solid phase syntheses are employed as more desirable methods to achieve large oligosaccharides because they take much shorter time for chemical processing (21, 22). However, solid phase syntheses are still limited by the large size of LM, and they can be done only on a relatively small scale.

To overcome the nature of numerous repeating units of mannose sugars in α(1–6) mannopyranan, polymerization is employed as an efficient method toward the synthesis of LM. A rapid and efficient synthesis of α(1–6) mannopyranan can be done via ring-opening polymerization, utilizing a tricyclic orthoester building block of mannose as a monomer (23). The chemically defined structure of α(1–6) mannopyranan will facilitate biological studies of LM interaction with host immune systems. Here, we report a rapid and efficient synthetic protocol toward the size-controlled α(1–6) mannopyranan (Figure 1).

Development of the regio-, stereo- and size-controlled synthesis of α(1–6) mannopyranan from the tricyclic orthoester building block of mannose 1.
Figure 1

Development of the regio-, stereo- and size-controlled synthesis of α(1–6) mannopyranan from the tricyclic orthoester building block of mannose 1.

The products of controlled polymerization, α(1–6) mannopyranan residues, containing different numbers of mannose units, can be used as intermediates toward the synthesis of LM. The resulting mannopyranans are already selectively protected at the position 2 of the backbone mannose units. Furthermore, α-mannosylation at the position 2 will yield the complex carbohydrate polymers found on LM. The access to LM glycans of various sizes will serve as a vital tool to determine whether and to what extent the number of mannose units in the LM backbone influences the magnitude of immune responses by mammalian cells. The detailed immunological studies of LM will lead to efficient treatment and prevention against TB.

2 Results and discussion

The synthetic route for the tricyclic orthoester building block of mannose and the methods for the ring-opening polymerization were developed based on a previously published report (Scheme 1) (23). The building block 3,4-O-benzyl-α-d-mannopyranose 1,2,6-orthobenzoate (1) was synthesized and utilized as a monomer in ring-opening polymerizations. The monomer contains a highly strained tricyclic structure, which is readily susceptible to ring-opening polymerizations upon activation with Lewis acids. Trimethylsilyl trifluoromethanesulfonate (TMSOTf) was introduced as an initiator because it gave the desired polymer products with regio- and stereoselectivity (23). Furthermore, the monomer treated with TMSOTf provided polymer products with narrow-molecular-weight distributions (23).

Synthetic protocols and characterization procedures for the controlled polymerization of monomer 1.
Scheme 1

Synthetic protocols and characterization procedures for the controlled polymerization of monomer 1.

For a rapid synthesis of size-controlled polymannosides, various chemical conditions were investigated in order to control the number of repeating mannose units on the LM backbone. Reaction temperature, reaction time, equivalent of catalyst as well as monomer concentration were varied for each set of polymerization conditions. The polymerization conditions were adjusted, based on the optimal polymerization conditions in a previously published report (23). In order to observe and account for all the products resulting from polymerizations, the polymer products were characterized by gel permeation chromatography (GPC), 1H and 13C in 1D and 2D NMR spectroscopy, optical rotation and melting point. The representative results of polymerizations under different reaction conditions are highlighted in Table 1.

Table 1

Results of polymerization reactions carried out at different experimental conditions.

The first parameter screened in the ring-opening polymerization of building block 1 is reaction temperature, which was varied from -80°C to room temperature (Table 1, entries 1–4). The reaction temperature could affect the reaction rate. At the same time, the reaction temperature may alter the stereoselectivity outcome of the polymer products. We observed no correlation between the degree of polymerization (DPn) and the reaction temperature. From these experiments, reaction temperature did not affect the number of monomers in the polymer product in the way we expected.

The reaction time was varied to monitor its effect on the number of mannose units in the polymer products. The reaction times were from 10 min to 24 h. Polymer products from all reaction conditions gave polysaccharides with high-molecular-weight distributions (Table 1, entries 5–8). The reaction time required to complete the ring-opening polymerization of building block 1 upon activation with Lewis acid is relatively short; therefore, the different reaction times did not affect the degree of polymerization of the products.

Furthermore, an initiator equivalent was employed as a parameter in controlling the size of polymer products. The equivalents of initiator were screened from 0.5 to 20 mol% (Table 1, entries 9–13). Stoichiometrically, we expected to obtain a larger size of polymer products when a smaller amount of the TMSOTf was used. However, the numbers of mannose units in the polymer products were not inversely proportional to the catalyst concentration. The lower equivalents of TMSOTf were probably inactivated by moisture contaminated in the chemical reactions more than the higher equivalents, resulting in premature termination of the polymerization reaction.

Another important reaction parameter screened in the polymerization reaction was monomer concentration. The concentrations were varied from 10 to 90 mg/100 μl of monomer 1 in CH2Cl2 (Table 1, entries 14–17). We observed a proportional correlation between the size (DPn) of the polymer products and the starting monomer concentration. At the monomer concentrations of 10 and 30 mg/100 μl, oligosaccharides were obtained as the major products. When the monomer concentrations increased, much larger polysaccharides were obtained as major products with high-percentage yields. In general, higher monomer concentrations result in higher molecular weights of α-d-mannopyranan polymer products. Higher monomer concentrations increase the rate of polymerization and, consequently, allow longer polymer chain growth before the termination step takes place. The polymerizations done at the monomer concentrations of 60 and 90 mg/100 μl (Table 1, entries 16–17) could provide long-chain polymers of the mannopyranan in comparable sizes to the LM backbones of Mtb.

The overall method to control the number of monomers in the polymer products in the ring-opening polymerization of building block 1 is summarized in Table 2. The monomer concentration can be manipulated to control the degree of polymerization of the polymer products.

Table 2

Overall effect of controlling parameters on the size of polymer products from the ring-opening polymerization.

Apart from being able to control polymer size, the polymer molecular weight distribution and the regio- and stereoselectivity are equally crucial. To facilitate further syntheses based on these α(1–6) mannopyranan intermediates and for the investigations on the biological properties of the mannopyranan products, the optimized polymerization conditions should give well size-, regio- and stereo-controlled products with a narrow-molecular-weight distribution. The homogeneity of the polymer products was verified by 1H, 13C NMR and GPC. Characterization by NMR spectroscopy of the products showed very similar spectra as in a previous report (23). The NMR J coupling constants between the anomeric carbon and the anomeric proton (JC13,H1) of the well-controlled polymer products from entries 16 and 17 are 171.3 and 171.1 Hz, respectively (13C-1H-coupled NMR spectra are shown in the supporting information). These coupling constants confirm the α glycosidic bonds in the polymer products (23). Figure 2A shows the GPC chromatogram of major products from the polymerization (Table 1, entry 17), while Figure 2B reveals less controlled polymer products. A narrow-molecular-weight distribution in a single GPC peak signifies a uniform-molecular-weight distribution of the polymer products.

GPC chromatograms of the polymer products: (A) well size-distribution-controlled polymer products from entry 17 of Table 1 with polydispersity index (Mw/Mn)=1.64; (B) less size-distribution-controlled polymer products from entry 4 of Table 1 with polydispersity index (Mw/Mn)=2.29.
Figure 2

GPC chromatograms of the polymer products: (A) well size-distribution-controlled polymer products from entry 17 of Table 1 with polydispersity index (Mw/Mn)=1.64; (B) less size-distribution-controlled polymer products from entry 4 of Table 1 with polydispersity index (Mw/Mn)=2.29.

3 Conclusion

In addition to the syntheses of regio- and stereo-controlled α(1–6) mannopyranan, syntheses of size-controlled α(1–6) mannopyranan by ring-opening polymerization were attempted by varying the reaction parameters including the reaction temperature, reaction time, catalyst loading and monomer concentration. The number of mannose units in α(1–6) mannopyranan may be controlled by the manipulation of the starting monomer concentration. Increases in monomer concentrations in the polymerization reaction resulted in higher molecular weights of α-d-mannopyranan polymer products. Different sizes of α(1–6) mannopyranan will be useful intermediates for further biological studies of LM interactions in mammalian hosts. Further detailed studies to exactly control the size of mannopyranans from the polymerization reaction are ongoing.

4 Experimental

4.1 General information

All chemicals used were of reagent grade and used as supplied except where noted. All reactions were performed in oven-dried glassware under an inert atmosphere unless noted otherwise. Dichloromethane (CH2Cl2) was dried over calcium hydride (CaH2) prior to use. Lutidine (TCI, Tokyo, Japan) was treated by potassium hydroxide (KOH), and allyl alcohol (Merck, Hohenbrunn, Germany) was treated with potassium carbonate (K2CO3) prior to use. Analytical thin layer chromatography was performed on Merck silica gel 60 F254 plates (0.25 mm, Darmstadt, Germany). Compounds were visualized by staining with cerium sulfate-ammonium molybdate (CAM) solution or phosphomolybdic acid solution. Flash column chromatography was carried out using forced flow of the indicated solvent on a Fluka Kieselgel 60 silica gel (230–400 mesh, MO, USA).

All new compounds were characterized by NMR spectroscopy (1H, 13C NMR and 2D NMR for some key intermediates) and high-resolution mass spectrometry (Bruker, microTOF, Bremen, Germany). NMR spectra were recorded on a Varian Gemini 2000 (200 MHz, CA, USA), Bruker AVANCE III (300 MHz, Bruker, Faellanden, Switzerland) Bruker AVANCE 400 (400 MHz) and Bruker AVANCE 600 (600 MHz), in CDCl3 with chemical shift referenced to internal standards CDCl3 (7.26 ppm for 1H and 77.0 ppm for 13C). Splitting patterns are indicated as s (singlet), bs (broad singlet), d (doublet) and m (multiplet) for 1H NMR data. NMR chemical shifts (δ) are reported in parts per million (ppm) and coupling constants (J) are reported in hertz. High-resolution mass spectral analyses were performed by the MS service at Chulabhorn Research Institute. Peaks are reported as m/z. Optical rotations were measured at 26°C using a JASCO P-1020 polarimeter (MD, USA). Melting points were measured in capillaries on a BŪCHI apparatus (model BŪCHI 535, Flawil, Switzerland). The average molecular weights (MW and MN) of the polymer were analyzed by GPC (Agilent, CA, USA) using HPLC-grade chloroform as an eluent. The eluent flow rate was kept constant at 0.5 ml/min. The temperature of the column was maintained at 40°C, while the detector was maintained at 35°C. Calibration curves were generated by using polystyrene standards (Shodex, NY, USA) with molecular weights of 3.9×106, 6.29×105, 6.59×104, 9.68×103 and 1.30×103 g/mol. The samples were dissolved and diluted with chloroform (0.5 mg/ml) and filtered before injection. The GPC analysis system was equipped with a universal styrene-divinylbenzene copolymer column (PLgel Mixed-C, 300×7.5 mm, 5 μm, Agilent, CA, USA), a differential refractometer detector (RI-G1362A, Agilent), an online degasser (G1322A, Agilent), an autosampler (G1329A, Agilent), a thermostatted column compartment (G1316A, Agilent) and a quaternary pump (G1311A, Agilent).

4.2 Polymerizations

The monomer used for the polymerizations were dried by using a Kugelrohr apparatus (Büchi GKR-51, Flawil, Switzerland) under high vacuum at 90°C for 24 h prior to use. Dichloromethane utilized as a solvent was transferred under inert atmosphere. To a solution of monomer in the solvent at the desired temperature (0°C by ice-water bath, -40°C by dry ice-acetonitrile bath and -80°C by dry ice-acetone bath), a catalytic amount of TMSOTf was added and the reaction was maintained at the desired temperature for the designated time. The reaction mixture was diluted with wet CH2Cl2 (not from distillation), washed with saturated aqueous NaHCO3 (3×), dried over anhydrous Na2SO4(s) and concentrated in vacuo. The crude product was dissolved in a minimum amount of CH2Cl2, and pentane was added until there was a white precipitate. The precipitate was allowed to settle overnight. After the mother liquor was removed, the precipitated polymer was dried under high vacuum to give a white powder.

4.2.1 Polymer products from entry 1 of Table 1

[α]Drt=+56.78 (c 0.1, 1 mg/ml, CHCl3); mp=105.0–111.8°C; 1H NMR (200 MHz, CDCl3) δ 3.30–4.24 (m, 5H), 4.26–4.52 (m, 2H), 4.70–4.98 (m, 2H), 5.07 (s, 1H), 5.88 (bs, 1H), 7.00–7.40 (m, 11H), 7.40–7.60 (m, 3H), 8.00–8.26 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 65.80, 68.56, 71.07, 71.41, 73.87, 75.11, 78.29, 98.65, 127.16, 127.42, 127.72, 127.93, 128.23, 128.39, 128.74, 129.93, 130.05, 133.37, 137.62, 138.55, 165.58.

4.2.2 Polymer products from Entry 2 of Table 1

[α]Drt=+58.40 (c 0.1, 1 mg/ml, CHCl3); mp=92.6–98.4°C; 1H NMR (200 MHz, CDCl3) δ 3.30–4.22 (m, 5H), 4.22–4.50 (m, 2H), 4.52–4.98 (m, 2H), 5.06 (s, 1H), 5.87 (bs, 1H), 7.00–7.38 (m, 11H), 7.42–7.60 (m, 3H), 8.04–8.26 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 66.00, 68.64, 71.16, 71.52, 73.98, 75.23, 78.41, 98.78, 128.47, 130.26, 133.75, 137.76, 138.73, 165.77.

4.2.3 Polymer products from entry 3 of Table 1

[α]Drt=+54.40 (c 0.1, 1 mg/ml, CHCl3); mp=100.3–106.8°C; 1H NMR (600 MHz, CDCl3) δ 3.23–4.00 (m, 5H), 4.10–4.45 (m, 2H), 4.53–4.76 (m, 2H), 4.88 (s, 1H), 5.68 (bs, 1H), 6.87–7.15 (m, 10H), 7.20–7.50 (m, 3H), 7.88–8.05 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 65.86, 68.53, 71.06, 71.30, 71.39, 73.86, 75.09, 75.24, 78.27, 98.65, 127.17, 127.22, 127.40, 127.44, 127.47, 127.52, 127.65, 127.69, 127.74, 127.83, 127.90, 128.08, 128.80, 128.15, 128.21, 128.23, 128.26, 128.31, 128.32, 128.38, 128.40, 128.45, 128.48, 128.56, 128.59, 128.62, 128.65, 128.72, 129.89, 129.94, 129.97, 130.06, 130.09, 130.13, 133.36, 137.64, 138.57, 165.63.

4.2.4 Polymer products from entry 4 of Table 1

[α]Drt=+55.19 (c 0.1, 1 mg/ml, CHCl3); mp=101.0–110.2°C; 1H NMR (300 MHz, CDCl3) δ 3.22–4.20 (m, 5H), 4.25–4.50 (m, 2H), 4.68–4.98 (m, 2H), 5.04 (s, 1H), 5.84 (bs, 1H), 6.94–7.37 (m, 11H), 7.40–7.62 (m, 3H), 8.00–8.25 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 65.63, 68.29, 70.82, 71.25, 73.64, 74.95, 78.16, 98.47, 126.93, 127.02, 127.25, 127.31, 127.50, 127.67, 127.72, 127.81, 127.97, 128.02, 128.09, 128.31, 128.35, 128.46, 128.62, 129.83, 129.92, 133.30, 137.43, 138.42, 165.48.

4.2.5 Polymer products from entry 5 of Table 1

[α]Drt=+58.99 (c 0.1, 1 mg/ml, CHCl3); mp=81.8–89.2°C; 1H NMR (400 MHz, CDCl3) δ 3.27–4.10 (m, 3H), 4.18–4.43 (m, 2H), 4.60–4.88 (m, 2H), 5.08 (s, 1H), 5.75 (bs, 1H), 6.91–7.55 (m, 12H), 7.95–8.14 (m, 2H).

4.2.6 Polymer products from entry 6 of Table 1

[α]Drt=+126.38 (c 0.1, 1 mg/ml, CHCl3); mp=68.9–89.2°C; 1H NMR (300 MHz, CDCl3) δ 3.28–3.85 (m, 3H), 3.85–4.12 (m, 2H), 4.22–4.50 (m, 2H), 4.67–4.92 (m, 2H), 5.03 (s, 1H), 5.84 (bs, 1H), 6.92–7.39 (m, 12H), 7.39–7.61 (m, 3H), 8.00–8.22 (m, 2H).

4.2.7 Polymer products from entry 7 of Table 1

[α]Drt=+120.12 (c 0.1, 1 mg/ml, CHCl3); mp=68.2–73.4°C; 1H NMR (400 MHz, CDCl3) δ 3.20–4.04 (m, 5H), 4.12–4.40 (m, 2H), 4.60–4.98 (m, 2H), 4.96 (s, 1H), 5.76 (bs, 1H), 6.85–7.55 (m, 17H), 7.96–8.20 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 68.28, 70.83, 71.24, 73.67, 74.94, 76.65, 78.15, 98.48, 126.94, 127.24, 127.64, 127.64, 128.08, 128.29, 128.60, 129.81, 129.94, 133.23, 138.43.

4.2.8 Polymer products from entry 8 of Table 1

[α]Drt=+68.19 (c 1.0, 10 mg/ml, CHCl3); mp=79.9–84.2°C; 1H NMR (300 MHz, CDCl3) δ 3.27–4.20 (m, 5H), 4.25–4.70 (m, 2H), 4.71–5.00 (m, 2H), 5.06 (s, 1H), 5.87 (bs, 1H), 6.90–7.42 (m, 12H), 7.42–7.70 (m, 3H), 8.00–8.35 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 65.62, 68.27, 70.79, 71.24, 73.62, 74.94, 78.16, 98.47, 126.90, 127.25, 127.68, 127.82, 128.03, 128.09, 128.32, 128.37, 128.62, 129.83, 129.91, 129.96, 133.33, 137.41, 138.42, 165.48.

4.2.9 Polymer products from entry 9 of Table 1

[α]Drt=+41.78 (c 1.0, 10 mg/ml, CHCl3); mp=86.7–90.2°C; 1H NMR (200 MHz, CDCl3) δ 3.33–4.18 (m, 5H), 4.26–4.69 (m, 2H), 4.74–4.98 (m, 2H), 5.05 (s, 1H), 5.80 (bs, 1H), 7.00–7.63 (m, 15H), 8.08–8.27 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 65.60, 68.17, 71.81, 74.60, 75.29, 98.15, 126.59, 127.25, 128.04, 128.67, 129.35, 129.59, 129.86, 131.00, 132.31, 134.33, 137.46, 138.40, 165.49.

4.2.10 Polymer products from entry 10 of Table 1

[α]Drt=+66.21 (c 0.1, 1 mg/ml, CHCl3); mp=118.3–125.8°C; 1H NMR (300 MHz, CDCl3) δ 3.33–3.83 (m, 3H), 3.90–4.12 (m, 2H), 4.25–4.53 (m, 2H), 4.74–4.96 (m, 2H), 5.07 (s, 1H), 5.85 (bs, 1H), 7.00–7.48 (m, 11H), 7.43–7.63 (m, 3H), 8.07–8.30 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 65.64, 67.17, 68.08, 69.36, 71.27, 71.73, 72.66, 74.53, 79.07, 97.25, 125.94, 126.65, 127.09, 127.26, 127.34, 127.91, 128.69, 129.05, 129.28, 129.36, 129.64, 129.90, 131.00, 132.29, 134.34, 137.41, 138.40, 165.48.

4.2.11 Polymer products from entry 11 of Table 1

[α]Drt=+55.84 (c 0.1, 1 mg/ml, CHCl3); mp=97.3–106.0°C; 1H NMR (300 MHz, CDCl3) δ 3.27–4.16 (m, 6H), 4.23–4.65 (m, 2H), 4.70–4.95 (m, 2H), 5.05 (s, 1H), 5.85 (bs, 1H), 6.96–7.65 (m, 15H), 8.00–8.30 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 65.64, 68.29, 70.80, 71.25, 73.62, 74.94, 78.16, 98.47, 126.93, 127.26, 127.67, 128.10, 128.31, 128.36, 128.62, 129.83, 129.92, 133.31, 137.42, 138.43, 165.49.

4.2.12 Polymer products from entry 12 of Table 1

[α]Drt=+56.84 (c 1.0, 10 mg/ml, CHCl3); mp=115.3–117.4°C; 1H NMR (300 MHz, CDCl3) δ 3.27–4.15 (m, 5H), 4.23–4.45 (m, 2H), 4.65–4.95 (m, 2H), 5.03 (s, 1H), 5.84 (bs, 1H), 6.94–7.40 (m, 11H), 7.40–7.61 (m, 3H), 8.00–8.24 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 65.68, 68.34, 70.85, 71.26, 73.67, 74.96, 78.17, 98.51, 126.97, 127.26, 127.33, 127.66, 127.81, 128.11, 128.31, 128.34, 128.62, 129.84, 129.96, 133.30, 137.47, 138.45, 165.50.

4.2.13 Polymer products from entry 13 of Table 1

[α]Drt=+38.79 (c 1.0, 10 mg/ml, CHCl3); mp=84.3–98.8°C; 1H NMR (200 MHz, CDCl3) δ 3.36–4.20 (m, 6H), 4.24–4.60 (m, 2H), 4.74–4.86 (m, 2H), 5.05 (s, 1H), 5.85 (bs, 1H), 6.96–7.40 (m, 14H), 7.40–7.60 (m, 3H), 8.02–8.22 (m, 2H).

4.2.14 Polymer products from entry 14 of Table 1

[α]Drt=+81.57 (c 0.1, 1 mg/ml, CHCl3); mp=91.5–98.7°C; 1H NMR (400 MHz, CDCl3) δ 3.22–4.10 (m, 4H), 4.15–4.40 (m, 2H), 4.60–4.85 (m, 2H), 4.95 (s, 1H), 5.75 (bs, 1H), 6.87–7.25 (m, 10H), 7.30–7.55 (m, 3H), 7.94–8.16 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 65.65, 68.30, 70.82, 71.14, 71.25, 73.64, 74.94, 78.15, 98.48, 126.96, 127.02, 127.25, 127.32, 127.54, 127.66, 127.76, 127.97, 128.02, 128.09, 128.30, 128.34, 128.47, 128.61, 129.82, 129.93, 133.30, 137.44, 138.43, 165.49.

4.2.15 Polymer products from entry 15 of Table 1

[α]Drt=+47.89 (c 1.0, 10 mg/ml, CHCl3); mp=83.7–90.3°C; 1H NMR (400 MHz, CDCl3) δ 3.26–4.00 (m, 7H), 4.17–4.42 (m, 2H), 4.64–4.88 (m, 2H), 4.96 (s, 1H), 5.76 (bs, 1H), 6.91–7.32 (m, 14H), 7.32–7.50 (m, 4H), 7.91–8.18 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 65.67, 68.32, 70.87, 71.26, 73.67, 74.96, 75.15, 78.16, 98.49, 126.97, 127.04, 127.67, 128.11, 128.19, 128.31, 128.48, 128.63, 129.84, 129.94, 133.31, 137.46, 138.44, 165.50.

4.2.16 Polymer products from entry 16 of Table 1

[α]Drt=+72.79 (c 1.0, 10 mg/ml, CHCl3); mp=99.4–103.5°C; 1H NMR (600 MHz, CDCl3) δ 3.25–4.10 (m, 5H), 4.20–4.53 (m, 2H), 4.66–4.96 (m, 2H), 5.03 (s, 1H), 5.83 (bs, 1H), 6.89–7.48 (m, 11H), 7.48–7.65 (m, 3H), 7.97–8.31 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 65.78, 68.46, 70.97, 71.32, 73.78, 75.02, 78.21, 98.58, 127.07, 127.14, 127.32, 127.68, 128.16, 128.20, 128.27, 128.34, 128.66, 129.87, 130.06, 133.30, 137.57, 138.51, 165.56.

4.2.17 Polymer products from entry 17 of Table 1

[α]Drt=+62.77 (c 1.0, 10 mg/ml, CHCl3); mp=100.1–104.3°C; 1H NMR (600 MHz, CDCl3) δ 3.26–4.15 (m, 5H), 4.20–4.53 (m, 2H), 4.65–4.96 (m, 2H), 5.04 (s, 1H), 5.85 (bs, 1H), 6.90–7.38 (m, 11H), 7.38–7.57 (m, 3H), 8.00–8.36 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 65.78, 68.46, 70.98, 71.34, 73.78, 75.04, 78.23, 98.60, 127.09, 127.15, 127.34, 127.42, 127.66, 127.70, 128.04, 128.07, 128.04, 128.07, 128.18, 128.20, 128.22, 128.29, 128.32, 128.34, 128.36, 128.38, 128.68, 129.89, 130.07, 133.33, 137.58, 138.52, 165.57.

Acknowledgments

We thank the Thailand Research Fund (TRF grant no. RSA5580059) and the Institute for the Promotion of Teaching Science and Technology (IPST) for financial support. We thank Mr. Paul Vincent Neilson for editing the original manuscript.

References

  • 1.

    Sohail M. Tuberculosis: a re-emerging enemy. J Mol Genet Med. 2006;2:87–8.PubMedGoogle Scholar

  • 2.

    Boshoff HI, Barry CE. Tuberculosis – metabolism and respiration in the absence of growth. Nat Rev Microbiol. 2005;3:70–80.CrossrefPubMedGoogle Scholar

  • 3.

    Telenti A, Iseman M. Drug-resistant tuberculosis: what do we do now? Drugs 2000;59:171–9.Web of ScienceGoogle Scholar

  • 4.

    Roy E, Lowrie DB, Jolles SR. Current strategies in TB immunotherapy. Curr Mol Med. 2007;7:373–86.PubMedCrossrefGoogle Scholar

  • 5.

    Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 1995;346:1339–45.Google Scholar

  • 6.

    Anderson P. Tuberculosis vaccines—an update. Nat Rev Microbiol. 2007;5:484.CrossrefWeb of ScienceGoogle Scholar

  • 7.

    Brennan PJ, Nikaido H. The envelope of mycobacteria. Annu Rev Biochem. 1995;64:29–63.PubMedCrossrefGoogle Scholar

  • 8.

    Cox HS, Morrow M, Deutschmann PW. Long term efficacy of DOTS regimens for tuberculosis: systematic review. Brit Med J 2008;336:484–7.Web of ScienceGoogle Scholar

  • 9.

    Yew WW, Leung CC. Management of multidrug-resistant tuberculosis: update 2007. Respirology 2008;13:21–46.Web of ScienceGoogle Scholar

  • 10.

    Yew WW, Chau CH. Drug-resistant tuberculosis in the 1990s. Eur Respir J. 1995;8:1184–92.CrossrefGoogle Scholar

  • 11.

    Pablos-Mendez A, Raviglione MC, Laszlo A, Binkin N, Rieder HL, Bustreo F, Cohn DL, Lambregts-van Weezenbeek CS, Kim SJ, Chaulet P, Nunn P. Global surveillance for antituberculosis-drug resistance, 1994–1997. World Health Organization-International Union Against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med. 1998;338:1641–9.Google Scholar

  • 12.

    Malm S, Walter K, Engel R, Maass S, Pfau S, Hübner G, Lindner B, Holst O, Ehlers S, Bange FC. In vitro and in vivo characterization of a Mycobacterium tuberculosis mutant deficient in glycosyltransferase Rv1500. Int J Med Microbiol. 2008;298:645–55.Google Scholar

  • 13.

    Berg S, Kaur D, Jackson M, Brennan PJ. The glycosyltransferases of Mycobacterium tuberculosis – roles in the synthesis of arabinogalactan, lipoarabinomannan, and other glycoconjugates. Glycobiology 2007;17:35–56R.PubMedCrossrefGoogle Scholar

  • 14.

    Chatterjee D, Khoo KH. Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects. Glycobiology 1998;8:113–20.CrossrefPubMedGoogle Scholar

  • 15.

    Brennan PJ. Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003;83:91–7.Google Scholar

  • 16.

    Vignal C, Guerardel Y, Kremer L, Masson M, Legrand D, Mazurier J, Elass E. Lipomannans, but not lipoarabinomannans, purified from Mycobacterium chelonae and Mycobacterium kansasii induce TNF-alpha and IL-8 secretion by a CD14-toll-like receptor 2-dependent mechanism. J Immunol. 2003;171:2014–23.Google Scholar

  • 17.

    Briken V, Porcelli SA, Besra GS, Kremer L. Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol Microbiol. 2004;53:391–403.Google Scholar

  • 18.

    Tamborrini M, Werz DB, Frey J, Pluschke G, Seeberger PH. Anti-carbohydrate antibodies for the detection of anthrax spores. Angew Chem Int Ed. 2006;45:6581–2.Google Scholar

  • 19.

    Werz DB, Seeberger PH. Total synthesis of antigen bacillus anthracis tetrasaccharide – creation of an anthrax vaccine candidate. Angew Chem Int Ed Engl. 2005;44:6315–8.CrossrefPubMedGoogle Scholar

  • 20.

    Seeberger PH, Werz DB. Synthesis and medical applications of oligosaccharides. Nature 2007;446:1046–51.Web of ScienceGoogle Scholar

  • 21.

    Plante OJ, Palmacci ER, Seeberger PH. Automated solid-phase synthesis of oligosaccharides. Science 2001;291:1523–7.Google Scholar

  • 22.

    Seeberger PH, Werz DB. Automated synthesis of oligosaccharides as a basis for drug discovery. Nat Rev Drug Discov. 2005;4:751–63.CrossrefPubMedGoogle Scholar

  • 23.

    Yongyat C, Ruchirawat S, Boonyarattanakalin S. Polymerization of mannosyl tricyclic orthoesters for the synthesis of alpha(1–6) mannopyranan – the backbone of lipomannan. Bioorg Med Chem. 2010;18:3726–34.Web of ScienceGoogle Scholar

Supplemental Material

The online version of this article (DOI: 10.1515/epoly-2014-0129) offers supplementary material, available to authorized users.

About the article

Corresponding author: Siwarutt Boonyarattanakalin, School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand, Tel.: +66 2 9869009 (ext. 2305), Fax: +66 2 9869009 (ext. 2301), e-mail: ,


Received: 2014-06-24

Accepted: 2014-09-28

Published Online: 2014-11-01

Published in Print: 2014-11-01


Citation Information: e-Polymers, Volume 14, Issue 6, Pages 383–390, ISSN (Online) 1618-7229, ISSN (Print) 2197-4586, DOI: https://doi.org/10.1515/epoly-2014-0129.

Export Citation

©2014 by De Gruyter.Get Permission

Supplementary Article Materials

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Haris Leelayuwapan, Somsak Ruchirawat, and Siwarutt Boonyarattanakalin
Carbohydrate Polymers, 2018
[2]
Warunda Bunthitsakda, Haris Leelayuwapan, Jiraporn Paha, Niwat Kangwanrangsan, Runglawan Chawengkirttikul, Marisa Ponpuak, Somsak Ruchirawat, and Siwarutt Boonyarattanakalin
Carbohydrate Polymers, 2018
[3]
Chakree Wattanasiri, Jiraporn Paha, Marisa Ponpuak, Somsak Ruchirawat, and Siwarutt Boonyarattanakalin
Carbohydrate Polymers, 2017
[4]
Harin Leelayuwapan, Niwat Kangwanrangsan, Runglawan Chawengkirttikul, Marisa Ponpuak, Ratthaphol Charlermroj, Kanokthip Boonyarattanakalin, Somsak Ruchirawat, and Siwarutt Boonyarattanakalin
The Journal of Organic Chemistry, 2017, Volume 82, Number 14, Page 7190
[5]
Nikita M. Podvalnyy, Alexander O. Chizhov, Alexander I. Zinin, and Leonid O. Kononov
Carbohydrate Research, 2016, Volume 431, Page 25

Comments (0)

Please log in or register to comment.
Log in