Convergent Route to ent-Kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α,6α-Diacetoxy-ent-kaura-9(11),16-dien-12,15-dione

Abstract

The Hoppe's homoaldol reaction of a cyclo-hexenyl carbamate with an aldehyde followed by an unprecedented BF·OEt mediated intramolecular Mukaiyama-Michael-type reaction affords the tetracyclic core structure of ent-kaurane diterpenoids. The usage of this convergent approach for assembling these natural products is demonstrated by the first asymmetric total syntheses of two highly oxidized ent-kaurane diterpenoids: Lungshengenin D and 1α,6α-diacetoxy-ent-kaura-9(11),16-dien-12,15-dione.

Enantioselective Total Syntheses of (+)-Fendleridine and (+)-Acetylaspidoalbidine

“…As shown in Scheme , our synthesis commenced with the formation of a multigram quantity of enaminone 13 by condensation of N -benzylaniline and 1,3-cyclohexanedione in toluene in the presence of p -TSA·H 2 O at reflux for 40 h. Subsequently, enaminone 13 was alkylated with LDA and allylchloroformate at −78 to 23 °C for 18 h to afford β-keto ester 14 in 62% yield. Alkylation of the β-keto ester 14 with tert -butyl­(2-iodoethoxy)­dimethylsilane was carried out in dimethylformamide (DMF) in the presence of Cs 2 CO 3 at 100 °C for 32 h to furnish a racemic keto ester 15 in 70% yield . For catalytic asymmetric allylation, we planned to utilize Pd 2 (dba) 3 in combination with ( S )- t -Bu-Phox ligand as the prior work by Stoltz and co-workers already established that ( S )- t -Bu-Phox provides the best enantioselectivity for allylation of enaminones .…”

Synthesis of Novel ent-Kaurane-Type Diterpenoid Derivatives Effective for Highly Aggressive Tumor Cells

“…The resulting compound 10 was reduced using NaBH 4 followed by acidification to produce compound 11 . Following the well- established Ma protocol [13], the key intermediate 12 (52%) was obtained (Scheme 1).…”

Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent‐Trachyloban‐3β‐ol, ent‐Trachyloban‐3‐one, Excoecarin E, and ent‐16α‐Hydroxy‐atisane‐3‐one

“…The bicyclo[3.2.1]‐ and bicyclo[2.2.2]‐octane subunits of ent ‐beyerane ( 5 ) and ent ‐atisane ( 6 ) could be accessed through the regioselective cyclopropane fragmentation of 7 [9] . While the synthesis of ent ‐kaurane ( 1 ) would require an intramolecular ether formation, [4f] we postulated that ent ‐trachylobane 7 could be realized through nucleophilic cyclopropanation [10] . Accordingly, dione 8 could serve as the common precursor.…”