Synthetic studies of rifamycins. VIII. An improved practical synthesis of the ansa-chain compounds for the rifamycin W synthesis

M. Nakata, Kazunobu Toshima, T. Kai, M. Kinoshita

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Abstract

The improved practical synthesis of 6,8,10-tri-O-acetyl-3-C-(acetoxymethyl)-3,5,7,9,11-pentadeoxy-1,2-O-isopro pylidene-5,7,9,11-tetra-C-methyl-L-erythro-D-altro-β-L-talo-dodecodialdof uranose-(1,4) 12-(diethyl acetal) (3), a useful synthetic segment for the rifamycin W ansa-chain, is described. The key intermediate, 3-O-benzyl-2,4,7-trideoxy-5,6-O-isopropylidene-2,4-di-C-methyl-aldehydo-D- glycero-D-allo-heptose (22), was synthesized in a 29.4% yield from methyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-α-D-altropyranoside (8) in 15 steps. The coupling of 22 with the lithium reagent prepared from butyllithium and 3-C-(benzyloxymethyl)-3,5,6-trideoxy-5-iodo-1,2-O-isopropylidene-α-D-ribo -5-hexenofuranose afforded only the 'Cram' product 24 in a 61% yield. The homogeneous hydrogenation of 24 with [RhCl(Ph3P)3] gave 8-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9,12-pentadeoxy-1,2:5,6-di-O-isopro pylidene-5,7,9-tri-C-methyl-D-erythro-D-altro-L-talo-dodecofuranose-(1,4) (25) and its C-5 epimer in 95 and 3.8% yields respectively. 6,8-Di-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9-tetradeoxy-1,2-O-isopropylid ene-5,7,9-tri-C-methyl-D-altro-β-L-talo-decodialdofuranose-(1,4), derived from 25 in a 91% yield, was subjected to coupling with 3,3-diethoxy-2-lithio-1-propene to afford about 1.7:1 excess of the 'Cram' product (30, 59% yield). The conversion of 30 into 3 was accomplished by the sequence of reactions involving homogeneous hydrogenation, debenzylation, and acetylation in a 75% yield. The 24-step synthesis of 3 from 8 was achieved in a 7% overall yield.

Original languageEnglish
Pages (from-to)3457-3464
Number of pages8
JournalBulletin of the Chemical Society of Japan
Volume58
Issue number12
Publication statusPublished - 1985

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Rifamycins
Hydrogenation
Heptoses
Acetylation
Acetals
Lithium
rifamycin SV
propylene

ASJC Scopus subject areas

  • Chemistry(all)

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Synthetic studies of rifamycins. VIII. An improved practical synthesis of the ansa-chain compounds for the rifamycin W synthesis. / Nakata, M.; Toshima, Kazunobu; Kai, T.; Kinoshita, M.

In: Bulletin of the Chemical Society of Japan, Vol. 58, No. 12, 1985, p. 3457-3464.

Research output: Contribution to journalArticle

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abstract = "The improved practical synthesis of 6,8,10-tri-O-acetyl-3-C-(acetoxymethyl)-3,5,7,9,11-pentadeoxy-1,2-O-isopro pylidene-5,7,9,11-tetra-C-methyl-L-erythro-D-altro-β-L-talo-dodecodialdof uranose-(1,4) 12-(diethyl acetal) (3), a useful synthetic segment for the rifamycin W ansa-chain, is described. The key intermediate, 3-O-benzyl-2,4,7-trideoxy-5,6-O-isopropylidene-2,4-di-C-methyl-aldehydo-D- glycero-D-allo-heptose (22), was synthesized in a 29.4{\%} yield from methyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-α-D-altropyranoside (8) in 15 steps. The coupling of 22 with the lithium reagent prepared from butyllithium and 3-C-(benzyloxymethyl)-3,5,6-trideoxy-5-iodo-1,2-O-isopropylidene-α-D-ribo -5-hexenofuranose afforded only the 'Cram' product 24 in a 61{\%} yield. The homogeneous hydrogenation of 24 with [RhCl(Ph3P)3] gave 8-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9,12-pentadeoxy-1,2:5,6-di-O-isopro pylidene-5,7,9-tri-C-methyl-D-erythro-D-altro-L-talo-dodecofuranose-(1,4) (25) and its C-5 epimer in 95 and 3.8{\%} yields respectively. 6,8-Di-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9-tetradeoxy-1,2-O-isopropylid ene-5,7,9-tri-C-methyl-D-altro-β-L-talo-decodialdofuranose-(1,4), derived from 25 in a 91{\%} yield, was subjected to coupling with 3,3-diethoxy-2-lithio-1-propene to afford about 1.7:1 excess of the 'Cram' product (30, 59{\%} yield). The conversion of 30 into 3 was accomplished by the sequence of reactions involving homogeneous hydrogenation, debenzylation, and acetylation in a 75{\%} yield. The 24-step synthesis of 3 from 8 was achieved in a 7{\%} overall yield.",
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AU - Kinoshita, M.

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N2 - The improved practical synthesis of 6,8,10-tri-O-acetyl-3-C-(acetoxymethyl)-3,5,7,9,11-pentadeoxy-1,2-O-isopro pylidene-5,7,9,11-tetra-C-methyl-L-erythro-D-altro-β-L-talo-dodecodialdof uranose-(1,4) 12-(diethyl acetal) (3), a useful synthetic segment for the rifamycin W ansa-chain, is described. The key intermediate, 3-O-benzyl-2,4,7-trideoxy-5,6-O-isopropylidene-2,4-di-C-methyl-aldehydo-D- glycero-D-allo-heptose (22), was synthesized in a 29.4% yield from methyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-α-D-altropyranoside (8) in 15 steps. The coupling of 22 with the lithium reagent prepared from butyllithium and 3-C-(benzyloxymethyl)-3,5,6-trideoxy-5-iodo-1,2-O-isopropylidene-α-D-ribo -5-hexenofuranose afforded only the 'Cram' product 24 in a 61% yield. The homogeneous hydrogenation of 24 with [RhCl(Ph3P)3] gave 8-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9,12-pentadeoxy-1,2:5,6-di-O-isopro pylidene-5,7,9-tri-C-methyl-D-erythro-D-altro-L-talo-dodecofuranose-(1,4) (25) and its C-5 epimer in 95 and 3.8% yields respectively. 6,8-Di-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9-tetradeoxy-1,2-O-isopropylid ene-5,7,9-tri-C-methyl-D-altro-β-L-talo-decodialdofuranose-(1,4), derived from 25 in a 91% yield, was subjected to coupling with 3,3-diethoxy-2-lithio-1-propene to afford about 1.7:1 excess of the 'Cram' product (30, 59% yield). The conversion of 30 into 3 was accomplished by the sequence of reactions involving homogeneous hydrogenation, debenzylation, and acetylation in a 75% yield. The 24-step synthesis of 3 from 8 was achieved in a 7% overall yield.

AB - The improved practical synthesis of 6,8,10-tri-O-acetyl-3-C-(acetoxymethyl)-3,5,7,9,11-pentadeoxy-1,2-O-isopro pylidene-5,7,9,11-tetra-C-methyl-L-erythro-D-altro-β-L-talo-dodecodialdof uranose-(1,4) 12-(diethyl acetal) (3), a useful synthetic segment for the rifamycin W ansa-chain, is described. The key intermediate, 3-O-benzyl-2,4,7-trideoxy-5,6-O-isopropylidene-2,4-di-C-methyl-aldehydo-D- glycero-D-allo-heptose (22), was synthesized in a 29.4% yield from methyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-α-D-altropyranoside (8) in 15 steps. The coupling of 22 with the lithium reagent prepared from butyllithium and 3-C-(benzyloxymethyl)-3,5,6-trideoxy-5-iodo-1,2-O-isopropylidene-α-D-ribo -5-hexenofuranose afforded only the 'Cram' product 24 in a 61% yield. The homogeneous hydrogenation of 24 with [RhCl(Ph3P)3] gave 8-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9,12-pentadeoxy-1,2:5,6-di-O-isopro pylidene-5,7,9-tri-C-methyl-D-erythro-D-altro-L-talo-dodecofuranose-(1,4) (25) and its C-5 epimer in 95 and 3.8% yields respectively. 6,8-Di-O-benzyl-3-C-(benzyloxymethyl)-3,5,7,9-tetradeoxy-1,2-O-isopropylid ene-5,7,9-tri-C-methyl-D-altro-β-L-talo-decodialdofuranose-(1,4), derived from 25 in a 91% yield, was subjected to coupling with 3,3-diethoxy-2-lithio-1-propene to afford about 1.7:1 excess of the 'Cram' product (30, 59% yield). The conversion of 30 into 3 was accomplished by the sequence of reactions involving homogeneous hydrogenation, debenzylation, and acetylation in a 75% yield. The 24-step synthesis of 3 from 8 was achieved in a 7% overall yield.

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