Total Synthesis of (−)-FD-838 and (−)-Cephalimysin A

Abstract

We completed a nine-step total synthesis of (−)-FD-838 and (−)-cephalimysin A. Our synthesis features a biogenetically guided assembly of the highly oxidized spirocyclic core by Snider-type tandem epoxidations of the chiral substrate derived from an amino acid derivative. Our synthetic approach provides a general and versatile solution to access spirocyclic PKS-NRPS-based secondary fungal metabolites.

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…Fluvirosaones A( 13)a nd B ( 14), pentacyclic securinega alkaloids recently isolated from Flueggea virosa,c onsist of ac yclopentenone Ering that is constructed by two carbon-carbon bond formations between the external three-carbon unit and the base securinega structure. [16] The a-tertiary amine moiety in the Ering poses added synthetic challenge.Itisimportant to note that unlike the aforementioned high-order and high-oxidation state securinega alkaloids,t he biosynthetic mode of assembly of the Ering in 13 and 14 is not obvious.F urthermore, 14 also possesses the rearranged aza-bicyclo-[3,3,1]-nonane core structure.T hese structural aspects raise interesting questions regarding the biogenetic origins of two closely related natural products.These structural and biosynthetic features of 12, 13, and 14,a sw ell as our interest in biosynthetically inspired synthesis of natural products, [17][18][19][20] led us to initiate asynthetic program aiming for these natural products from readily available securinega precursors.…”

Highly Oxidized γ-Lactam-Containing Natural Products: Total Synthesis and Biological Evaluation

“…In the presence of triethylamine, 302 and isobutyl glyoxal (286) were reacted to produce tautomers 303/304, which were used in the next reaction without purification because of their instability. Han's group reported the total syntheses of berkeleyamide D (142), 92 azaspirene (133), 93 FD-838 (141), 94 and cephalimysin A (138) 94 based on a strategy inspired by the biosynthetic origin of azaspirene 95 and the biomimetic synthesis of α,β-unsaturated γ-hydroxy-γ-lactam and α,β-epoxy-γ-hydroxy-γ-lactam ring systems reported by the Snider group. 96 Initially, they achieved the total synthesis of berkelyamide D (142) (Scheme 27).…”

“…Finally, they achieved the total syntheses of FD-838 (141) and cephalimysin A (138) by chiral pool synthesis (Scheme 29). 94 These total syntheses used β-ketoester 318, the appropriate aldehyde 268 or 324, and amine 327, which contains two chiral centers. Spiro compounds consisting of an inseparable mixture of 330 and 331 or 332 were obtained in same manner as the previous azaspirene synthesis.…”

One‐pot two‐step synthesis of fused thiazinofuranone linked geminal bis 1,2,3‐triazole hybrids and their in vitro cytotoxic screening

“…Furanones and their fused frameworks are versatile heterocyclic moieties that exist in many natural products [1,2] and biologically active compounds [3]. In particular, 2,2-di substituted furanone core is present in many natural products such as Pseurotin A [4], Hyperolactone C [5,6], Trachyspic acid [7,8], Jatrophone [9], Eremantholide A [10], Cephalimysin A [11], Geiparvarin [12,13], Bullatenone [14] Griseofulvin [15] and have been discovered to possess a broad range of medicinal applications [3] and also used for the synthesis of fluorescent materials [16].…”