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. 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.

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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.
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References

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