Facile total synthesis of the antimalarial nonenolide

The facile total synthesis of the antimalarial nonenolide 1 is reported. The convergent strategy features the use of reactions such as Sharpless asymmetric dihydroxylation, aldol addition, Mitsunobu reaction, and ring-closing metathesis (RCM).

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(S)-1-((Hex-5-en-2-yloxy)methyl)-4-methoxybenzeneC14H20O2[α]D25=+22 (c 2.0, CHCl3)Source of chirality: (S)-propylene oxideAbsolute configuration: (S)

(2S,5R)-5-(Methoxymethoxy)hept-6-en-2-olC9H18O3[α]D25=+13 (c 0.3, CHCl3)Absolute configuration: (2S,5R)

(S)-4-Benzyl-3-((2S,3R)-3-(tert-butyldimethylsilyloxy)-2-(methylthio)pent-4-enoyl)oxazolidin-2-oneC22H33NO4SSiEe >98% [by chiral HPLC][α]D25=+28.6 (c 3.45, CHCl3)Source of chirality: Evans Aldol reactionAbsolute configuration: (S,2S,3R)

(S)-((2R,5R)-5-(Methoxymethoxy)hept-6-en-2-yl) 3-(tert-butyldimethylsilyloxy)pent-4-enoateC20H38O5Si[α]D25=+39.6 (c 4.0, CHCl3)Source of chirality: Mitsunobu reactionAbsolute configuration: (S,2S,5R)