Intramolecular [2+2] photocycloaddition reactions as an entry to the 2-oxatricyclo[4.2.1.0(4,9)]nonan-3-one skeleton of lactiflorin.
Two [2+2] photocycloaddition routes were evaluated as possible ways to access the tricyclic core structure found in the terpene monoglycoside lactiflorin. While the first route via γ-substituted cyclopentenones was quickly discarded, the reactions of racemic (5R*)-3-benzyloxy-5-but-3'-enyl-4-methoxycarbonylfuran-2(5H)-ones proceeded in high yields and with perfect diastereoselectivity. However, it turned out that the regioselectivity was strongly dependent on the substitution pattern within the but-3'-enyl chain, which connects the terminal olefinic double bond to the photoexcited butenolide chromophor. If the chain was unsubstituted or if a tert-butyldimethylsilyloxy group was placed at the 2' position in a syn-relationship to the existing stereogenic center (5R*,2'S*), the crossed product prevailed with regioselectivities of 89:11 to 69:31. If the tert-butyldimethylsilyloxy group was positioned at 2' in an anti-relationship to the existing stereogenic center (5R*,2'R*), the desired straight products were obtained in regioselectivities of 74:24 to 55:45 (61-83% yield). Following this route, the aglycon part of lactiflorin was obtained by an intramolecular [2+2] photocycloaddition and a subsequent hydrogenolysis in 53% yield. Its further conversion into the natural product after glycosylation included a methyl addition to the lactone carbonyl group, which was optimized to give the desired key intermediate in a yield of 70%. The further conversion to lactiflorin was achieved in four steps and with an overall yield of 49%.
Department Chemie and Catalysis Research Center, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.
Ping
P
Lu
Eberhardt
E
Herdtweck
Thorsten
T
Bach
D000473:Alkanes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry*; D006031:Glycosylation; D008968:Molecular Conformation; D039821:Monoterpenes / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000473:Alkanes; D006027:Glycosides; D039821:Monoterpenes; C494902:lactiflorin; C017573:nonane