Enantioselective total synthesis of (-)-triptolide, (-)-triptonide, (+)-triptophenolide, and (+)-triptoquinonide.
The first enantioselective total synthesis of (-)-triptolide (1), (-)-triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc)3, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)-Triptophenolide methyl ether (5) was then prepared in > 99% enantiomeric excess (> 99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral beta-keto esters 17 (without an alpha-substituent) and 17a (with an alpha-chloro substituent).
Yang
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Department of Chemistry, University of Hong Kong, Hong Kong.
Ye
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Xu
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D018360:Crystallography, X-Ray; D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004852:Epoxy Compounds; D010616:Phenanthrenes; D013237:Stereoisomerism; D014315:Triterpenes / Q000138:chemical synthesis*
D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D010616:Phenanthrenes; D014315:Triterpenes; C408127:triptoquinonide; C001899:triptolide; C084079:triptonide; C035061:triptophenolide