Asymmetric total synthesis of antiviral agents (+)-sattazolin and (+)-sattabacin

Abstract

The concise enantioselective total synthesis of antiviral agents (+)-sattazolin and (+)-sattabacin are described in six steps. This synthetic strategy started from commercially available isovaleraldehyde and the key reactions involved in this synthesis are Sharpless epoxidation, phenyl Grignard, Eu(III) catalyzed ring opening of chiral epoxide with indole.

Chemistry and Biology of Acyloin Natural Products

“…The acyloin 4-hydroxysattabacin (7) has been shown to be an intermediate in the biosynthesis of discoipyrrole natural products 32 (see Figure 3). 4-Hydroxysattabacin (7) and enol 47 were isolated alongside discoipyrroles A-D (43)(44)(45)(46) from Bacillus hunanensis. 32 The discoipyrroles are discodin domain receptor (DDR2) signalling pathway inhibitors.…”

“…Discoipyrroles A-D (43-46) showed cytotoxicity against mutant lung cancer cells (non-small-cell lung cancer line HCC366) in the M range. 7) is incorporated into discoipyrrole A (43), and by analogy sattabacin ( 5) is incorporated into discoipyrrole B (44). This led MacMillan and co-workers to perform both a one-pot total synthesis of 43 in organic solvent, and a synthesis by treating the starting materials 7, 48, and 55 with spent bacterial media, both strongly suggesting a non-enzymatic process.…”

“…The Narsaiah group 44 reported concise asymmetric syntheses of sattazolin A ( 14 ) and ( S )-sattabacin ( 5a ) hinging on a ring opening of epoxide 95 (Scheme 18 ). Sharpless asymmetric epoxidation and concomitant kinetic resolution of racemic alcohol 93 afforded epoxide 94 in 44% yield, which was oxidised and converted into acetal 95 .…”