[structure: see text] An ester dienolate [2,3]-Wittig rearrangement was utilized to access the alkylated citric acid skeleton 6 that is characteristic for the viridiofungins and other members of the alkyl citrate family of secondary natural products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the rearrangement product (+/-)-syn-16 in moderate yield and with very good diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the viridiofungins. Amide formation between the racemic viridiofungin precursors 35a-c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by preparative reversed-phase HPLC provided the isopropyl dimethyl ester of viridiofungin A ((+)-39a), A2 ((+)-39b), and A4 ((+)-39c) as well as the nonnatural diastereomers (-)-38a-c.

A catalytic asymmetric Claisen rearrangement (CAC) in concert with a ring-closing metathesis (RCM) has been utilized in the enantioselective synthesis of the C10-C18 segment of ecklonialactone B.(-)-Ecklonialactone B (E B , 1), is a carbocyclic C 18 -oxylipin of marine origin that has been isolated from the brown algae Ecklonia stolonifera 1 and Egregia menziessi 2 (Scheme 1). 3 E B is a member of a larger family of ecklonialactones that are distinguished by the number and position of double bonds in the macrolactone ring. 4,5 Furthermore, the cyclopentane segment of ecklonialactones may either be epoxidized (as in E B ) or trans-dihydroxylated at the C12/C13 position. The relative configuration of ecklonialactone A (D 6,9 ), E A , has been established by crystal structure analysis. 1 By chemical correlation, it was demonstrated that E B (D 9 ) possesses the same relative configuration as E A . 1 The absolute configuration of E A was later deduced from its chiroptical properties and conferred to E B based on the similar negative optical rotation values of E A and E B . 2 As part of a program aimed at the exploration of the scope and limitations of the recently developed catalytic asymmetric Claisen rearrangement (CAC) 6 in natural product synthesis, 7 E B (1) was identified as a worthwhile target molecule. Specifically, the proof of the assigned absolute configuration, which has important biosynthetic implications, 2 as well as the study of potential biological activities 3 of 1 and its derivatives appear appealing. In this letter, we report an 11-step synthesis (8% overall yield) of the enantiomerically pure cyclopentanoid 2, the key building block in the total synthesis of E B (1).Our retrosynthetic analysis of E B (1) is depicted in Scheme 1. It is apparent that the molecular complexity of 1 materializes at the highly substituted cyclopentane moiety, which features five contiguous stereogenic carbon atoms, and that the cyclopentanoid 2 represents an advanced building block toward E B (1). The first retrosynthetic simplification converts 2 into the cyclopentanoid 3 by removing the epoxide and C18. Subsequent utilization of a ring-closing metathesis transformation and of a redox transformation provides the a-keto ester 4. The following disconnection rests on the CAC retron present in 4 and provides the achiral E,Z-configured allyl vinyl ether 5. The final simplification takes advantage of the availability of an olefination transformation for the diastereoselective synthesis of 2-alkoxycarbonyl-substituted allyl vinyl ethers as 5 from the known phosphonoacetate 6. 7bScheme 1 Retrosynthesis of (-)-ecklonialactone B (1) The synthesis of the allyl vinyl ether (E,Z)-5 is summarized in Scheme 2. Nucleophilic ring opening of tetrahydrofurane by the phenyl selenide anion, that was generated from diphenyl diselenide (7) and lithium aluminum hydride (LAH) 8 followed by Parikh-Doering oxidation, 9 provided the aldehyde 8. Horner-WadsworthEmmons olefination 10 of the aldehyde 8 utilizing the 2-allyloxy-substituted trimethyl...

Synthesis: Synthetic Studies Toward (-)-Ecklonialactone B. -The enantioselective synthesis of the C10-C18 segment (V) of ecklonialactone B (VI) is described. -(WANG, Q.; MILLET, A.; HIERSEMANN*, M.; Synlett 2007, 11,