Asymmetric total synthesis of onoseriolide, bolivianine, and isobolivianine.
In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations.
Key Laboratory of Green Chemistry and Technology of the Ministry of Education Institution, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064 (China), Fax: (+86) 28-8541-3712.
Biao
B
Du
Changchun
C
Yuan
Tianzi
T
Yu
Li
L
Yang
Yang
Y
Yang
Bo
B
Liu
Song
S
Qin
D000081008:Bicyclic Monoterpenes; D002384:Catalysis; D003500:Cyclization; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D011789:Quantum Theory; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry
D000081008:Bicyclic Monoterpenes; D012717:Sesquiterpenes; D013729:Terpenes; C524834:bolivianine; C551646:onoseriolide; C052875:verbenone
chiral resolution; density functional calculations; natural products; synthetic methods; total synthesis