Total synthesis of the antifungal antibiotic PF1163A

The total synthesis of a novel antifungal antibiotic PF1163A is reported utilising Keck asymmetric allylation, Sharpless kinetic resolution, regioselective epoxide-ring opening, esterification and ring-closing metathesis as the key reactions.

Figure optionsDownload as PowerPoint slide

(3R,5S)-5-(Benzyloxy)oct-1-en-3-olC15H22O2[α]D25=+62.2 (c 0.54, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (3R,5S)

(S)-Methyl 3-[4-(allyloxy)phenyl]-2-[tert-butoxycarbonyl(methyl)amino]propanoateC19H27NO5[α]D25=-173.9 (c 0.4, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (2S)

(S)-Methyl 2-[tert-butoxycarbonyl(methyl)amino]-3-[4-(2-hydroxyethoxy)phenyl]propanoateC18H27NO6[α]D25=-93.6 (c 0.4, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (2S)

{(2S,3S)-3-[5-(tert-Butyldiphenylsilyloxy)pentyl]oxiran-2-yl}methanolC24H34O3SiEnantiomeric excess: 88.76%[α]D25=-32.4 (c 1.2, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (2S,3S)

(R)-tert-Butyl(6-methyloct-7-enyloxy)diphenylsilaneC25H36OSi[α]D25=-9.7 (c 1.1, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (6R)

(R)-6-Methyloct-7-en-1-olC9H18O[α]D25=-17.3 (c 1.3, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (6R)

(R)-6-Methyloct-7-enoic acidC9H16O2[α]D25=-35.9 (c 0.2, CHCl3)Source of chirality: stereoselective synthesisAbsolute configuration: (6R)

(S)-((3R,5S)-5-(Benzyloxy)oct-1-en-3-yl) 3-(4-(2-(benzyloxy)ethoxy)phenyl)-2-(methylamino)propanoateC39H51NO7[α]D25=-50.2 (c 0.1, CHCl3)Source of chirality: l-tyrosine and stereoselective synthesisAbsolute configuration: (2S,3R,5S)

(S)-[(3R,5S)-5-(Benzyloxy)oct-1-en-3-yl] 3-[4-(2-(benzyloxy)ethoxy)phenyl]-2-[(R)-N,6-dimethyloct-7-enamido]propanoateC43H57NO6[α]D25=-32.4 (c 0.2, CHCl3)Source of chirality: l-tyrosine and stereoselective synthesisAbsolute configuration: (2S,3R,5S,6R)

(3S,10R,13S)-3-[4-(2-Hydroxyethoxy)benzyl]-13-[(S)-2-hydroxypentyl]-4,10-dimethyl-1-oxa-4-azacyclotridecane-2,5-dioneC27H43NO6[α]D25=-89.3 (c 0.5, MeOH)Source of chirality: l-tyrosine and stereoselective synthesisAbsolute configuration: (3S,10R,13S,2S)