Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar 16;72(6):1931-40.
doi: 10.1021/jo061991n. Epub 2007 Feb 3.

Synthetic 3-O-methylmannose-containing polysaccharides (sMMPs): design and synthesis

Margaret C Hsu  1 , Jinhwa Lee, Yoshito Kishi
Affiliations

Synthetic 3-O-methylmannose-containing polysaccharides (sMMPs): design and synthesis

Margaret C Hsu et al. J Org Chem. .

Erratum in

  • J Org Chem. 2007 May 11;72(10):3980

Abstract

With the hope of mimicking the chemical and biological properties of natural 3-O-methylmannose-containing polysaccharides (MMPs), synthetic 3-O-methylmannose-containing polysaccharides (sMMPs) were designed and synthesized in a convergent manner. With little modification of the Mukaiyama glycosidation, high alpha-selectivity (>50:1 approximately >20:1) and yields (79 approximately 74%) were achieved for the key glycosidation steps. The exceptionally high alpha-selectivity observed was shown to be consequent to the selective anomerization of beta- to alpha-anomer under the glycosidation conditions. This glycosidation is well suited for a highly convergent oligosaccharide synthesis, particularly because of excellent chemical yields even when using approximately equal-sized donors and acceptors in an approximately 1:1 molar ratio. An iterative reaction sequence allowed the growing oligosaccharide to double in size after each cycle and led to an efficient synthesis of sMMP 8-, 12-, and 16-mers 18-20.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of mycobacterial polysaccharides 3-O-methyl-D-mannose-containing polysaccharides (MMP) and 6-O-methyl-D-glucose-containing lipopolysaccharides (MGLP)/6-O-methyl-D-glucose-containing polysaccharides (MGP).
Figure 2
Figure 2
Structures of synthetic analogs of mycobacterial polysaccharides, sMMP (synthetic polysaccharides composed of 3-O-methyl-D-mannose) and sMGP (synthetic polysaccharides composed of 6-O-methyl-D-glucose).
Figure 3
Figure 3
1H NMR spectra of the MeO signals of 13 (400 MHz, CDCl3). Reaction A was quenched after 21.5 h; Reaction B was quenched after 9.5 h.
Scheme 1
Scheme 1
Reagents and conditions: (a) 1. Sc(OTf)3, Allyl-OH, 80%; 2. PhCH(OMe)2, HBF4, 83%; (b) 1. n-Bu2SnO, MeOH, 83%; 2. MeI, 74%; (c) 1. NaH, BnBr, imidazole, 66%; 2. TiCl4, NaBH3CN, 73%.
Scheme 2
Scheme 2
Reagents and conditions: (a) TMSOTf, Et3N, 98%; (b) 1. protection with R; 2. (i) (Ph3P)3RhCl, DABCO; (ii) HCl; 3. mono-methyl phthalate, EDCI, DMAP; (c) SnCl4-AgClO4 (10 mol%), 0 °C.
Scheme 3
Scheme 3
Products formed from β-7d under the Mukaiyama glycosidation conditions.
Scheme 4
Scheme 4
Reaction pathways of mannosyl donor (6d) and acceptor (5) under the Mukaiyama glycosidation conditions.
Scheme 5
Scheme 5
Reagents and conditions: (a) SnCl4-AgClO4, Et2O, 0 °C, 76%.
Scheme 6
Scheme 6
Reagents and conditions: (a) 1. (i) (Ph3P)3RhCl, DABCO; (ii) HCl, 81%; 2. mono-methyl phthalate, EDCI, DMAP, 98%; (b) 1. NaOH, MeOH, 92%; 2. TMSOTf, Et3N, 99%; (c) SnCl4-AgClO4, Et2O, −20 °C→0 °C, 76%.
Scheme 7
Scheme 7
Reagents and conditions: (a) 1. (i) (Ph3P)3RhCl, DABCO; (ii) HCl, 81%; 2. mono-methyl phthalate, EDCI, DMAP, 100%; (b) 1. NaOH, MeOH, 92%; 2. TMSOTf, Et3N, 85%; (c) SnCl4-AgClO4, Et2O, −20 °C→0 °C, 79%.
Scheme 8
Scheme 8
Reagents and conditions: (a) 1. NaOH, MeOH, 83%; 2. TMSOTf, Et3N, 100%; (b) SnCl4-AgClO4, Et2O, 0 °C, 75%.
Scheme 9
Scheme 9
Reagents and conditions: (a) 1. (i) (Ph3P)3RhCl, DABCO; (ii) HCl, 77%; 2. mono-methyl phthalate, EDCI, DMAP, 94%; (b) 1. NaOH, MeOH, 83%; 2. TMSOTf, Et3N, 100%; (c) SnCl4-AgClO4, Et2O, 0 °C, 74%.
Scheme 10
Scheme 10
Reagents and conditions: (a) 1. NaOH, MeOH; 2. Pd(OH)2 on C, H2.
Scheme 11
Scheme 11
Reagents and conditions: (a) SnCl4-AgClO4, Et2O. Note: 12-mer was synthesized via a combination of donor 4-mer and acceptor 8-mer.
See this image and copyright information in PMC

References

    1. For reviews on MMP and MGLP/MGP, see: Bloch K. Advances in Enzymology. 1977;45:1.Ballou CE. Accts Chem Res. 1968;1:366.Ballou CE. Pure Appl Chem. 1981;53:107.

    1. For isolation and structural characterization of MMP, see: Gray GR, Ballou CE. J Biol Chem. 1971;246:6835.Maitra SK, Ballou CE. J Biol Chem. 1977;252:2459.Weisman LS, Ballou CE. J Biol Chem. 1984;259:3457.Weisman LS, Ballou CE. J Biol Chem. 1984;259:3464.Ilton M, Jevans AW, McCarthy ED, Vance D, White HB, III, Bloch K. Proc Natl Acad Sci USA. 1971;68:87.

    1. For isolation and structural characterization of MGLP/MGP, see: Lee YC, Ballou CE. J Biol Chem. 1964;239:PC3602.Saier MH, Jr, Ballou CE. J Biol Chem. 1968;243:4332.Smith WL, Ballou CE. J Biol Chem. 1973;248:7118.Forsberg LS, Dell A, Walton DJ, Ballou CE. J Biol Chem. 1982;257:3555. Regarding the structural heterogeneity of MGP, Ballou commented that at least two forms of MGP containing 21 hexoses exist: Kamisango K, Dell A, Ballou CE. J Biol Chem. 1987;262:4580. Also see, Tuffal G, Albigot R, Monsarrat B, Ponthus C, Picard C, Rivière M, Puzo G. J Carbohydr Chem. 1995;14:631.

    1. The structure of MG(L)P shown in Figure 1 is the revised structure suggested by Rivière based on the structure of polysaccharide isolated from Mycobacterium bovis BCG. See: Tuffal G, Albigot R, Rivière M, Puzo G. Glycobiology. 1998;8:675–684.

    1. Flick PK, Bloch K. J Biol Chem. 1974;249:1031. - PubMed

Publication types