Control of olefin geometry in the bryostatin B-ring through exploitation of a C(2)-symmetry breaking tactic and a Smith-Tietze coupling reaction.
A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon for the bryostatin family of antitumor agents is reported. Noteworthy features of our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13 en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson etherification reaction completed the synthesis of 2.
Hale
K J
KJ
The Christopher Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom.
Hummersone
M G
MG
Bhatia
G S
GS
D000475:Alkenes / Q000737:chemistry* / Q000378:metabolism; D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D054713:Bryostatins; D004852:Epoxy Compounds / Q000378:metabolism; D004987:Ethers / Q000378:metabolism; D006801:Humans; D007659:Ketones / Q000378:metabolism; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D000475:Alkenes; D000970:Antineoplastic Agents; D054713:Bryostatins; D004852:Epoxy Compounds; D004987:Ethers; D007659:Ketones; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1