Synthesis of lactam and acetamido analogues of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide

• Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-2-deoxy-2-tetrachlorophthalimido-β-D- glucopyranoside (15) with the donors ethyl 3,4-di-O-acetyl-6-O-benzyl-2- deoxy-2-[[(2,2,2-trichloroethoxy)carbonyl]amino]-1-thio-β-D- galactropyranoside (14), 4-methylphenyl 2,3-di-O-acetyl-4-azido-6-O-benzyl- 4-deoxy-1-thio-β-D-galactopyranoside (30), and 4-methylphenyl 2-O-acetyl-4- azido-6-O-benzyl-4-deoxy-3-O-(methoxyethanoyl)-1-thio-β-D-galactopyranoside (44) gave the lactose-diamine derivatives 16, 33, and 45, respectively. Fucosylation of the NHAc derivatives of 16 and 33 (17 and 34) with the donor 18 gave, after deprotection and N-acetylation, the 2-NHAc-Le(x) and 4-NHAc- Le(x) trisaccharides 3 and 5, respectively. Removal of the Troc group from the tetrasaccharide intermediate 23, followed by N-acetylation (→ 24), gave the NHAc-SLe(x) tetrasaccharide 2. Regioselective sialylation of the partially protected trisaccharide diols 21 and 37 with the sialyl donors 22 and 38 gave, after deprotection and lactamization, the SLe(x)-1'''→2'- lactam 1 and the SLe(x)-1'''→4'-lactam 4, respectively. The stannylidene acetal of the trisaccharide diol 21 was regioselectively 3-O-alkylated with tert-butyl bromoacetate; reductive removal of the Troc protecting group and addition of methanolic MeONa caused formation of a lactam ring. Compound 40 was thus obtained over four steps in an overall yield of 52%. Deprotection of 40 furnished the Le(x)-3,2-lactam 6 in 74% yield. Fucosylation of the lactose-diamine derivative 46 with donor 18 gave the N3-Le(x) trisaccharide derivative 47. The azido function of 47 was reduced with H2S, which caused spontaneous closure of a lactam ring. Removal of the protecting groups then gave the Le(x)-3,4-lactam 7. The total yields of 1, 2, 3, 4, 5, and 7 from the monosaccharide starting materials 14, 15, 18, 22, 30, 38, and 44 were 10%, 10%, 22%, 14%, 62%, and 28%, respectively.

Ämnesord

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

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