Total, asymmetric synthesis of ethyl D-ido-4-heptulosuronate derivatives starting from diethyl 4-oxopimelate

Bromination of diethyl 4-oxopimelate, followed by double elimination of HBr and ketalization provided diethyl (E,E)-4,4-(ethylidenedioxy)hepta-2,5-dienedioate 4. Sharpless asymmetric dihydroxylation of 4 produced diethyl (2S,3S)-4,4-(ethylidenedioxy)-2,3-dihydroxyhept-5-eneiodate (+)-5, with 78% e.e. The corresponding tetrol could not be obtained in one step. Silylation of (+)-5 and a second asymmetric dihydroxylation, followed by silylation led to 20% of meso-diester 9 and 60% of diethyl (2S,3S,5S,6S)-2,3,5,6-tetrakis[(t-butyl) 4,4-(ethylidenedioxy)heptanedioate (-)-10. Reductive desymmetrization of (-)-10 with DIBAL-H furnished, after selective oxidation, ethyl (2S,3S,5S,6S)-2,3,5,6-tetrakis-[(t-butyl oxoheptanoate (+)-13 which was then converted into ethyl 1,2,3,6-0-tetraacetyl-4,4-ethylidenedioxy-alpha- and beta-D-ido-heptapyranuronate (-)-15 alpha,beta and into the corresponding 3-(alpha-D-pyranosyl)propene (-)-16. (C) 1999 Elsevier Science Ltd. All rights reserved

Synthesis of a C29-C51 Subunit of Spongistatin 1 (Altohyrtin A) Starting from (R)-3-Benzyloxy-2-methylpropan-1-ol

A protected C29-C51 subunit ((+)-38) of Spongistatin 1 has been obtained. Key steps involve the aldol condensation of (3S,4R)-3-methyl-7-[(paramethoxybenzyl)oxy]-4-[(triethylsilyl)oxy]octan-2-one ((-)-6) with (tert-butyl)dimethylsilyl 4-deoxy-2,3-di-O-(methoxymethyl)-4-methyl-6-O-(tert-butyl)dimethylsilyl)--D-glycero-L-gluco-heptodialdo-1,5-pyranoside ((+)-7), and a C-glycosidation of (4R,7R&S,E)-7,8-dichloro-2-methylidene-1-(trimethylsilyl)oct-5-en-4-yl paramethoxybenzoate (16). Aldehyde (+)-7 was derived from (R)-3-benzyloxy-2-methylpropan-1-ol ((+)-10) in 13 formal steps but requiring the isolation of 5 intermediate products only. The longest linear synthetic scheme converts (+)-10 into (+)-38 in 2% overall yield (isolation of 11 intermediate products)