A silicon controlled total synthesis of the antifungal agent (+)-preussin

β‐Silylacrylate as a Multipurpose Reagent in Organic Synthesis

“…The synthesis of densely functionalized pyrrolidinol based bioactive natural products can be accessed from β‐silylacrylates. Ghosh and co‐workers have reported the total synthesis of (+)‐preussin ( 56 ; Scheme 21), [80–82] starting from β‐SA ( E )‐ 1c . Michael addition of dimethyl malonate (DMM) to β‐silylacrylate followed by Krapcho demethoxycarbonylation of the derived triester gave the diester 50a ( Scheme 21).…”

“…The acid 53 was then converted to ketone 54 in good yield through mixed pivaloic anhydride formation and reaction with nonylmagnesium bromide. The ketone 54 was converted to all cis pyrrolidine 55 in a few steps wherein the silicon group played crucial role in anti alkylation of the ester enolate, Si‐facilitated Pb(OAc) 4 mediated oxidation of amide to urethane and catalytic hydrogenation [80,81] . Silicon to hydroxy conversion [27] with retention of configuration gave the alcohol which was converted to (+)‐preussin ( 56 ) in overall good yield.…”

β‐Silylmethylene Malonate as Versatile Reagent in Organic Synthesis

“…Synthesis of β‐silylated keto‐ester 25 a has previously been achieved by a relatively lengthy process [62a] from 3‐[dimethyl(phenyl)silyl]glutaric anhydride 22 by asymmetric desymmetrization with Evans’ oxazolidinones [62b,c] and used in the total synthesis of pyrrolidine based natural product (+)‐preussin 29 (Scheme 24). [61a,b] …”

“…Silylated ketodiesters could be easily converted to respective silylated ketoesters 25 b – e in very good yields by Krapcho deethoxycarbonylation (Scheme 27). [65] The keto ester 25 b , the ethyl ester version of 25 a which has already been converted to (+)‐preussin 29 (see; Scheme 24) wherein a silicon directed alkylation, Si‐accelerated Curtius reaction, silicon directed hydrogenation and stereospecific conversion of PhMe 2 Si group to the desired hydroxyl group with retention of configuration were the key steps [61a,b] …”

Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (−)-Preussin B, and 3-Deoxy-(+)-preussin B

“…A large number of these rely on derivatization of readily available chiral pool materials: elaboration of l -phenylalanine facilitated the second synthesis of (+)-preussin that was reported, and this material (or derivatives thereof) has proven to be the most popular starting material by far in subsequent syntheses, − although (in chronological order) d -phenylalanine, d -arabinose, l -aspartic acid, l -pyroglutaminol, , l -serine, , and ( S )-malic acid , (or derivatives thereof) have also been employed as the sources of chirality. Other de novo asymmetric syntheses have been developed, − along with one formal synthesis of (+)-preussin − and two syntheses of (−)-preussin. , Moreover, the synthesis of all eight possible stereoisomers (using an enantiopure phenylalanine derivative as the starting material, proceeding via two nonselective reactions and chromatographic separation) has been reported, − as well as one synthesis of (±)-preussin. , The truncated analogue (+)-preussin B, (2 S ,3 S ,5 R )- N (1)-methyl-2-benzyl-5-(1′-heptyl)­pyrrolidin-3-ol (Figure ), was isolated [along with (+)-preussin] in 2014 from Simplicillium lanosoniveum TAMA 173 and was shown to exhibit weak antifungal activity . The first and, to date, the only synthesis of (+)-preussin B to be reported is that of Huang et al, who employed ( S )-malic acid as their starting material .…”