Synthetic Studies on Biscembranoids. Asymmetric Total Synthesis of the 14-Membered Diene Unit of Methyl Sarcophytoate

Minoru Yasuda, Mitsuaki Ide, Yuka Matsumoto, Masaya Nakata

Research output: Contribution to journalArticle

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Abstract

An asymmetric total synthesis of the 14-membered diene unit, (1S,2S,4E,6E,10S,11Z,14R)-10,14-epoxy-4-isopropenyl-1,7,11-trimethyl-4,6,11- cyclotetradecatnene-1,2-diol (3), of methyl sarcophytoate (1) has been achieved. Methyl ketone, (3S,4S)-3,4-(isopropylidenedioxy)-3,7-dimethyl-6-octen-2-one (6), was enantioselectively prepared from geraniol via Sharpless asymmetric epoxidation and a regioselective epoxide-opening reaction. The aldol coupling between the lithium enolate of 6 and aldehyde, (2E,6E)-2,6-dimethyl-8-(2,2-dimethylpropanoyloxy)-2,6-octadienal (7), which was also prepared from geraniol, gave a 1 : 1 separable mixture of the adducts (17 and 18). Reduction of the carbonyl group in 17 and 18, followed by regioselective oxidation of the allylic hydroxy group, afforded α,β-unsaturated ketone, (2E, 6E,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-10-hydroxy-11,12- (isopropylidenedioxy)-3,7,1,15-tetramethyl-2,6,14-hexadecatrien-8-one (5). The intramolecular oxy-Michael addition of 5 followed by regioselective enol inflation and deoxygenation gave dihydropyran, (2E,6S,7Z,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-6,10-epoxy-11,12-(isopropyl- idenedioxy)-3,7,11,15-tetramethyl-2,7,14-hexadecatriene (31). The regioselective epoxidation of 31 and a subsequent functional-group transformation gave (2E,6S,7Z,10R,11R,12S,4RS)-6,10:14,15-diepoxy-11,12-(isopropylidenedioxy)-3, 7,11,15-tetramethyl-1-(phenylthio)-2,7-hexadecadiene (4). The 14-membered ring formation was achieved by the treatment of 4 with the n-BuLi-Bu 2Mg complex to give (1Z,3S,6E,8RS,9RS,11S,12R,13R)-3,13-epoxy-9-(1-hydroxy-1-methylethyl)-11,12- (isopropylidenedioxy)-2,6,12-trimethyl-8-(phenylthio)-1,6-cyclotetradecadiene (33), which was transformed to 3 through triene construction and deacetonidation.

Original languageEnglish
Pages (from-to)1417-1429
Number of pages13
JournalBulletin of the Chemical Society of Japan
Volume71
Issue number6
Publication statusPublished - 1998 Jun

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Epoxidation
Ketones
Epoxy Compounds
Lithium
Aldehydes
Functional groups
Oxidation
methyl sarcophytoate
geraniol
3-hydroxybutanal
n-butyllithium

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Synthetic Studies on Biscembranoids. Asymmetric Total Synthesis of the 14-Membered Diene Unit of Methyl Sarcophytoate. / Yasuda, Minoru; Ide, Mitsuaki; Matsumoto, Yuka; Nakata, Masaya.

In: Bulletin of the Chemical Society of Japan, Vol. 71, No. 6, 06.1998, p. 1417-1429.

Research output: Contribution to journalArticle

Yasuda, Minoru ; Ide, Mitsuaki ; Matsumoto, Yuka ; Nakata, Masaya. / Synthetic Studies on Biscembranoids. Asymmetric Total Synthesis of the 14-Membered Diene Unit of Methyl Sarcophytoate. In: Bulletin of the Chemical Society of Japan. 1998 ; Vol. 71, No. 6. pp. 1417-1429.
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abstract = "An asymmetric total synthesis of the 14-membered diene unit, (1S,2S,4E,6E,10S,11Z,14R)-10,14-epoxy-4-isopropenyl-1,7,11-trimethyl-4,6,11- cyclotetradecatnene-1,2-diol (3), of methyl sarcophytoate (1) has been achieved. Methyl ketone, (3S,4S)-3,4-(isopropylidenedioxy)-3,7-dimethyl-6-octen-2-one (6), was enantioselectively prepared from geraniol via Sharpless asymmetric epoxidation and a regioselective epoxide-opening reaction. The aldol coupling between the lithium enolate of 6 and aldehyde, (2E,6E)-2,6-dimethyl-8-(2,2-dimethylpropanoyloxy)-2,6-octadienal (7), which was also prepared from geraniol, gave a 1 : 1 separable mixture of the adducts (17 and 18). Reduction of the carbonyl group in 17 and 18, followed by regioselective oxidation of the allylic hydroxy group, afforded α,β-unsaturated ketone, (2E, 6E,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-10-hydroxy-11,12- (isopropylidenedioxy)-3,7,1,15-tetramethyl-2,6,14-hexadecatrien-8-one (5). The intramolecular oxy-Michael addition of 5 followed by regioselective enol inflation and deoxygenation gave dihydropyran, (2E,6S,7Z,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-6,10-epoxy-11,12-(isopropyl- idenedioxy)-3,7,11,15-tetramethyl-2,7,14-hexadecatriene (31). The regioselective epoxidation of 31 and a subsequent functional-group transformation gave (2E,6S,7Z,10R,11R,12S,4RS)-6,10:14,15-diepoxy-11,12-(isopropylidenedioxy)-3, 7,11,15-tetramethyl-1-(phenylthio)-2,7-hexadecadiene (4). The 14-membered ring formation was achieved by the treatment of 4 with the n-BuLi-Bu 2Mg complex to give (1Z,3S,6E,8RS,9RS,11S,12R,13R)-3,13-epoxy-9-(1-hydroxy-1-methylethyl)-11,12- (isopropylidenedioxy)-2,6,12-trimethyl-8-(phenylthio)-1,6-cyclotetradecadiene (33), which was transformed to 3 through triene construction and deacetonidation.",
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T1 - Synthetic Studies on Biscembranoids. Asymmetric Total Synthesis of the 14-Membered Diene Unit of Methyl Sarcophytoate

AU - Yasuda, Minoru

AU - Ide, Mitsuaki

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N2 - An asymmetric total synthesis of the 14-membered diene unit, (1S,2S,4E,6E,10S,11Z,14R)-10,14-epoxy-4-isopropenyl-1,7,11-trimethyl-4,6,11- cyclotetradecatnene-1,2-diol (3), of methyl sarcophytoate (1) has been achieved. Methyl ketone, (3S,4S)-3,4-(isopropylidenedioxy)-3,7-dimethyl-6-octen-2-one (6), was enantioselectively prepared from geraniol via Sharpless asymmetric epoxidation and a regioselective epoxide-opening reaction. The aldol coupling between the lithium enolate of 6 and aldehyde, (2E,6E)-2,6-dimethyl-8-(2,2-dimethylpropanoyloxy)-2,6-octadienal (7), which was also prepared from geraniol, gave a 1 : 1 separable mixture of the adducts (17 and 18). Reduction of the carbonyl group in 17 and 18, followed by regioselective oxidation of the allylic hydroxy group, afforded α,β-unsaturated ketone, (2E, 6E,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-10-hydroxy-11,12- (isopropylidenedioxy)-3,7,1,15-tetramethyl-2,6,14-hexadecatrien-8-one (5). The intramolecular oxy-Michael addition of 5 followed by regioselective enol inflation and deoxygenation gave dihydropyran, (2E,6S,7Z,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-6,10-epoxy-11,12-(isopropyl- idenedioxy)-3,7,11,15-tetramethyl-2,7,14-hexadecatriene (31). The regioselective epoxidation of 31 and a subsequent functional-group transformation gave (2E,6S,7Z,10R,11R,12S,4RS)-6,10:14,15-diepoxy-11,12-(isopropylidenedioxy)-3, 7,11,15-tetramethyl-1-(phenylthio)-2,7-hexadecadiene (4). The 14-membered ring formation was achieved by the treatment of 4 with the n-BuLi-Bu 2Mg complex to give (1Z,3S,6E,8RS,9RS,11S,12R,13R)-3,13-epoxy-9-(1-hydroxy-1-methylethyl)-11,12- (isopropylidenedioxy)-2,6,12-trimethyl-8-(phenylthio)-1,6-cyclotetradecadiene (33), which was transformed to 3 through triene construction and deacetonidation.

AB - An asymmetric total synthesis of the 14-membered diene unit, (1S,2S,4E,6E,10S,11Z,14R)-10,14-epoxy-4-isopropenyl-1,7,11-trimethyl-4,6,11- cyclotetradecatnene-1,2-diol (3), of methyl sarcophytoate (1) has been achieved. Methyl ketone, (3S,4S)-3,4-(isopropylidenedioxy)-3,7-dimethyl-6-octen-2-one (6), was enantioselectively prepared from geraniol via Sharpless asymmetric epoxidation and a regioselective epoxide-opening reaction. The aldol coupling between the lithium enolate of 6 and aldehyde, (2E,6E)-2,6-dimethyl-8-(2,2-dimethylpropanoyloxy)-2,6-octadienal (7), which was also prepared from geraniol, gave a 1 : 1 separable mixture of the adducts (17 and 18). Reduction of the carbonyl group in 17 and 18, followed by regioselective oxidation of the allylic hydroxy group, afforded α,β-unsaturated ketone, (2E, 6E,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-10-hydroxy-11,12- (isopropylidenedioxy)-3,7,1,15-tetramethyl-2,6,14-hexadecatrien-8-one (5). The intramolecular oxy-Michael addition of 5 followed by regioselective enol inflation and deoxygenation gave dihydropyran, (2E,6S,7Z,10R,11R,12S)-1-(2,2-dimethylpropanoyloxy)-6,10-epoxy-11,12-(isopropyl- idenedioxy)-3,7,11,15-tetramethyl-2,7,14-hexadecatriene (31). The regioselective epoxidation of 31 and a subsequent functional-group transformation gave (2E,6S,7Z,10R,11R,12S,4RS)-6,10:14,15-diepoxy-11,12-(isopropylidenedioxy)-3, 7,11,15-tetramethyl-1-(phenylthio)-2,7-hexadecadiene (4). The 14-membered ring formation was achieved by the treatment of 4 with the n-BuLi-Bu 2Mg complex to give (1Z,3S,6E,8RS,9RS,11S,12R,13R)-3,13-epoxy-9-(1-hydroxy-1-methylethyl)-11,12- (isopropylidenedioxy)-2,6,12-trimethyl-8-(phenylthio)-1,6-cyclotetradecadiene (33), which was transformed to 3 through triene construction and deacetonidation.

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