Total Synthesis of TK‐57‐164A, Isariotin F, and Their Putative Progenitor Isariotin E

Abstract

Keeping it simple: A simple strategy for the total synthesis of three complex natural products has been developed, while also confirming the putative generation of 1 and 2 from 3. The benefits of a simple dissymmetric 2,5‐cyclohexadienone are illustrated and provide the foundation for rapid diastereoselective functionalization leading to the first total synthesis of these compounds.

A Strategy for the Late-Stage Divergent Syntheses of Scyphostatin Analogues

“…7 Treatment of this compound with lithium hydroxide induced saponification of both the O -Boc and methyl ester residues. The crude acid was next subjected to amide bond formation with N , O -dimethylhydroxylamine hydrochloride using standard peptide coupling conditions (Scheme 2).…”

“…We had previously demonstrated the successful introduction of two hydrides and rearrangement during our synthesis of the isariotins. 7 Because the rearrangement would require the subsequent use of a strong acid, however, we felt it prudent to perform the exchange of the acid-labile vinyl TMS residue for the iodide substituent now rather than later. Exposure of lactone 6 to the conditions developed by Zakarian and coworkers cleanly afforded iodide 27 in 77% yield.…”

“…In addition, large quantities of vinylogous ester 6 could be obtained from the reduction, deprotection, oxidative dearomatization, and subsequent epoxidation of ester 7 . 7 …”

Hypervalent iodine reagents in the total synthesis of natural products

“…277 The same group also described the oxidative ipso-cyclization of a nitro group toward the synthesis of spironitronates, 278 and scyphostatin analogues.…”

Diastereoselective Spiroannulation of Phenolic Derivatives: Effect of Steric Hindrance on the Diastereoselectivity

“…The spiroannulation (or spirocyclization) of simple 4-substituted phenols has been known for more than 50 years, (Cha et al, 2009;Frie et al, 2009;Moriarty et al, 2001;Pierce et al, 2008) yet the asymmetric version of the reaction in which the stereochemistry of the newly formed spirocarbon is controlled lack in examples. For the past 10 years our focus has been to develop methods to accomplish the asymmetric spiroannulation of simple phenols in order to use these methods in the asymmetric synthesis of natural products such as the Aranorosins (Mukhopadhyay et al, 1997;Roy et al, 1992;Watanabe et al, 2003), Gymnastatins (Amagata et al, 1998a;Amagata et al, 1998b;Numata et al, 1997;Phoon et al, 2004) and Manumycins (Hu et al, 2001;Sattler et al, 1998).…”