A Ring Contraction Strategy toward a Diastereoselective Total Synthesis of (+)-Bakkenolide A

Abstract

A diastereoselective route to (+)-bakkenolide A is presented from the readily available optically active Wieland-Miescher ketone. This novel synthesis of this sesquiterpene lactone features the following as key stereoselective transformations: (i) the ring contraction reaction of a octalone mediated by thallium(III) nitrate (TTN); (ii) a hydrogenation to create the cis-fused junction; and (iii) the formation of the C7 quaternary center through an enolate intermediate. Furthermore, during this work, the absolute configuration of a trinorsesquiterpene isolated from Senecio humillimus was assigned.

Hypervalent iodine reagents in the total synthesis of natural products

“…Examples include the synthesis of (+)-bakkenolide A (Scheme 73) 332 and rubrolone aglycon. 333 This α-hydroxylation can be stereoselective, as described in the synthesis of nakiterpiosinone (Scheme 57), 214 seragakinone A, 334 (─)-7-deoxydaunomycinone, 335 and formal total synthesis of (─)-cephalotaxine (Scheme 58).…”

“…However, in 1989 Stork and Zhao 374 reported that PIFA can be used in this transformation. This iodine(III) reagent has been used in an efficient manner during the total synthesis of several natural products, including cembranes (Scheme 71), 245 (±)-uleine (Scheme 72), 375 lyngbouilloside macrolactone core, 376 peribysin E, 377 (+)-bakkenolide A (Scheme 73), 332 and rapamycin. 166 The deprotection using PIFA can also be performed using an alcohol as solvent, directly delivering an acetal.…”

Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

“…Existing pharmacology tests suggest that BA could markedly inhibit the proliferation of several tumor lines cells, such as HepG2 and HeLa with an ED50 at about 0.8 and 1.0 µg/mL, respectively, indicating its anti‐tumor potential. Several practical synthesis methods have been developed for the total synthesis of bakkenolide‐A . Considering the potential bioactivity of BA and the availability of the pure compound, BA has been selected in our lab for further and comprehensive investigation in terms of its pharmacological activity.…”

“…Several practical synthesis methods have been developed for the total synthesis of bakkenolide-A. [17,18] Considering the potential bioactivity of BA and the availability of the pure compound, BA has been selected in our lab for further and comprehensive investigation in terms of its pharmacological activity.…”

Identification of Intermediates in the Biosynthesis of PR Toxin by Penicillium roqueforti

“…[19,20] Similar to the reported procedure for the synthesis of petasin, [21] 15 was subsequently used in an aldol addition to acetone to yield ligudicin C( 16), ak nown natural product from Ligularia dictyoneura. [22] Tr eatment with triflic anhydride in NEt 3 was followed by …”