Total Synthesis of Spirotenuipesines A and B

Abstract

Spirotenuipesines A and B, isolated from the entomopathogenic fungus Paecilomyces tenuipes by Oshima and co-workers, have been synthesized. The synthesis features the highly stereoselective construction of two vicinal all-carbon quaternary centers (C5 and C6) via an intramolecular cyclopropanation/radical initiated fragmentation sequence and a diastereoselective intermolecular Diels−Alder reaction between α-methylenelactone dienophile 20 and synergistic diene 6a. Installation of the C9 tertiary alcohol occurred via nucleophilic methylation. An RCM reaction to produce a tetrasubstituted double bond in the presence of free allylic alcohol and homoallylic oxygenated functional group is also described. This route shortened the synthesis of 11 from 9 steps to 3 steps. We have further developed a strategy to gain access to optically active spirotenuipesines A and B through the synthesis of enantioenriched 10 from commercially available R-(−)-epichlorohydrin.

Asymmetric Synthesis of Hispidanin A and Related Diterpenoids

“…Inspired by our success in the model study on the radical cascade polycyclization, we initiated the asymmetric total synthesis of the diene 5 with the epoxide 39 ( Scheme ), which was prepared from commercially available (+)‐epichlorohydrin in two steps by following the known procedure . Epoxide‐opening by alkynyl lithium and subsequent silyl protection afforded compound 63 , along with only a small amount of compound 64 .…”

“…-4 [d] Fe(acac) 3 PhSiH 3 EtOH 71 %1 :1.5:0 5 [d] Fe ( Inspired by our success in the model study on the radical cascade polycyclization, we initiated the asymmetric total synthesis of the diene 5 with the epoxide 39 (Scheme 11), which was prepared from commercially available (+ +)-epichlorohydrin in two steps by following the known procedure. [21] Epoxideopeningb ya lkynyll ithium and subsequents ilyl protection afforded compound 63,a longw ith only as mall amount of compound 64.Am ild hydration protocol was developed to fully converta lkyne 63 to ester 64 with 0.5 mol %o fA u(PPh 3 )Cl in the absence of as ilver salt. [22] Other catalysts, such as HgCl 2 , HCl, AuCl 3 ,a nd Sc(OTf) 3 ,l ed to deprotection of the TBS ether and formationo falactone as the side product.…”

Neurotrophic Natural Products: Chemistry and Biology

“…[178] In this approach the tricyclic motif of 190 was formed through a Cu II -promoted intramolecular cyclo-propanation. [179] This was followed by a radical deoxygenation under Barton–McCombie conditions, which also cleaved the strained cyclopropane ring of 190 to afford 191 .…”

Neurotrophe Naturstoffe – ihre Chemie und Biologie

“…[176] Das Zwischenprodukt 184 wurde danach in das Alkin 185 überführt, aus dem durch intramolekulare Pauson-Khand-Reaktion [85] [177] Der Arbeitsgruppe von Danishefsky gelang auch eine Synthese der (AE)-Spirotenuipesine A (180) und B (181) (Schema 30). [178] Durch Cu II -vermittelte intramolekulare Cyclopropanierung [179]…”