De Novo Asymmetric Approach to Aspergillide‐C: Synthesis of 4‐epi‐seco‐Aspergillide‐C

Abstract

An asymmetric approach toward the synthesis of the marine natural product aspergillide‐C has been developed. The convergent asymmetric synthesis uses two asymmetric Noyori transfer hydrogenations to enantioselectively prepare the two key fragments, a C‐1 to C‐7 pyranone fragment and a C‐8 to C‐14 β‐keto‐sulfone fragment. The absolute stereochemistry of the pyranone fragment was established by a Noyori reduction of β‐furylketoester to form a furyl alcohol. An Achmatowicz rearrangement was used to stereoselectively convert the furyl alcohol in to the key pyranone fragment. The absolute stereochemistry of the β‐keto‐sulfone fragment was established by a Noyori reduction of an ynone to form a propargyl alcohol. An alkyne zipper isomerization was used to stereospecifically convert the propargyl alcohol in to the β‐keto‐sulfone fragment. Finally, a Pd‐catalyzed C‐glycosylation was used to diastereoselectively couple the two fragments, which when combined with a reduction and Julia‐Kocienski type elimination formed a protected variant of the 4‐epi‐seco‐acid of aspergillide‐C.

Exploring a De Novo Route to Bradyrhizose: Synthesis and Isomeric Equilibrium of Bradyrhizose Diastereomers≠

“…Specifically the C-4 ketone in Pd-πallyl B imparts the requisite electrophilicity to react with unactivated alcohols. [27][28][29][30][31][32][33] Thus, we were pleasantly surprised with the overall facility of this vinylogous pyranone palladium(0)-glycosylation (via Pd-π-allyl A), as it compared well to the parent variant (via Pd-π-allyl B) in terms of reactivity with unactivated alcohols, and regio-and stereoselectivity.…”

“…Previously, we have found than the C‐4 ketone plays a critical role in reactivity and the overall efficiency of the pyranone variant of the palladium(0)‐glycosylation. Specifically the C‐4 ketone in Pd‐π‐allyl B imparts the requisite electrophilicity to react with unactivated alcohols [27–33] . Thus, we were pleasantly surprised with the overall facility of this vinylogous pyranone palladium(0)‐glycosylation (via Pd‐π‐allyl A ), as it compared well to the parent variant (via Pd‐π‐allyl B ) in terms of reactivity with unactivated alcohols, and regio‐ and stereoselectivity.…”

De novoasymmetric Achmatowicz approach to oligosaccharide natural products

“…Key to the assembly of these building blocks is the use of a Pd-glycosylation reaction. 15,30 This highly diastereoselective process occurs with retention of configuration converting pyranones 4 (α- l ), 4 (β- l ), 4 (α- d ), and 4 (β- d ) with a C -1 BocO-leaving group into C -1 O -glycosides 5 (α- l ), 5 (β- l ), 5 (α- d ), and 5 (β- d ), with an anomeric alkoxy-group. This approach has also been extended to a Pd-cyclitolization (5a-carbasugar glycosylation).…”

“…9 Finally, a Pd-catalyzed glycosylation [10][11][12] is used to stereospecifically transfer the pyranone to various glycosyl acceptors (e.g., N-, O-, C-nucleophiles). [13][14][15] The reaction occurs rapidly and in high yields for all four stereoisomers, with the enone acting as an anomeric directing group (via a Pd-p-allyl). 16 This approach mechanistically stands in contrast to the use of silver and Au, which appears to occur via a Lewis acid glycosylation mechanism.…”