Synthesis of the C10–C24‐Bis‐Spiroacetal Core of 13‐Desmethyl Spirolide C Based on a Sila‐Stetter‐Acetalization Process

Abstract

Synthesis of the bis-spiroacetal core of 13-desmethyl spirolide C has been completed based on a sila-Stetter-acetalization process. The acylsilane and enone partners in the Stetter reaction were prepared in 7 and 11 steps, respectively, from (S) and (R)-aspartic acid. The quaternary center at C19 in the enone moiety was controlled by relying on the Seebach's chiral self-reproduction method using an enantiopure (S)-lactic acid based dioxolanone. The final acid-catalyzed spiroacetalization provided the desired spiroacetal as a mixture of diastereoisomers in 13 linear steps. Whatever the conditions used, the non-natural transoid isomer was formed preferentially. However, both cisoid and transoid isomers were isolated pure and their structure assigned unambiguously through NMR spectroscopic studies.

Synthesis of the C4–C16 Polyketide Fragment of Portimines A and B

“…Pleasingly, indantrione 30 With the successful establishment of the C4−C16 polyketide fragment 12, we were interested to study the intramolecular ketalization of this fragment to gain some knowledge of the [6.2.1]-ring system in portimine A (1). Inspired by literature precedent, 46,47 compound 12 was initially treated with a catalytic amount of camphorsulfonic acid to induce TBS deprotection and concomitant intramolecular ketalization (Scheme 5). However, only the diketone 40 was isolated.…”

Stereoselective Total Synthesis of Aspergillide A: A Visible Light-Mediated Photoredox Access to the Trisubstituted Tetrahydropyran Core

“…Our synthesis commenced with the preparation of radical acceptor 12 . Treatment of known epoxide 11 with trimethylsulfonium iodide and n BuLi afforded allylic alcohol 12 in an excellent yield (95%). Next, the key iodolactonization was tested.…”

Synthesis and biology of cyclic imine toxins, an emerging class of potent, globally distributed marine toxins

“…84 This approach utilizes a sila-Stetter reaction in a convergent assembly of the spiroketalization precursor. As in previous approaches, acid-catalyzed thermodynamic spiroketalization generally favors the undesired diastereomer.…”

“…Very recently, another effective approach to the spiroketal subunit of 13-desmethyl spirolide C was reported by the Landais and Desvergnes group. 84 This approach utilizes a sila-Stetter reaction in a convergent assembly of the spiroketalization precursor. As in previous approaches, acid-catalyzed thermodynamic spiroketalization generally favors the undesired diastereomer.…”