Total synthesis of (+/-)-scopadulin.
The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. A highly stereoselective cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the sterically hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols. Finally, the total synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16 and modification of the C-4 alpha-functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated methylation for the generation of a tertiary axial alcohol at C-16 is extremely high.
Rahman
S M
SM
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ohno
H
H
Murata
T
T
Yoshino
H
H
Satoh
N
N
Murakami
K
K
Patra
D
D
Iwata
C
C
Maezaki
N
N
Tanaka
T
T
D000998:Antiviral Agents / Q000138:chemical synthesis; D004224:Diterpenes / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism
D000998:Antiviral Agents; D004224:Diterpenes; C064856:scopadulin