Synthesis and spectroscopic correlation of the diastereoisomers of 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid: implications for the structures of papuamides A–D and mirabamides A–D

All 4 diastereomeric possibilities for the 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid (Dhtda) residue, found in the cyclic depsipeptide natural products papuamides A–D and mirabamides A–D, were stereoselectively synthesized using a Z-selective Wittig reaction of both enantiomers of 2,4-dimethylhex-2-enyl-triphenylphosphonium bromide with all four diastereoisomers of ethyl-3-formyl-2-methyl-1,4-dioxaspiro[4,4]nonane-2-carboxylate. To elucidate the configuration of Dhtda, the 1H and 13C NMR spectra of the synthetic isomers were compared to those of the natural residue. On the basis of that comparison, it is suggested that the likely configuration of the diastereomer present in Dhtda residue is either (2R,3S,8S) or (2S,3R,8S) in the papuamides and mirabimides.

Figure optionsDownload as PowerPoint slide

Ethyl (2E,4S)-2,4-dimethyl-2-hexenoateC10H18O2Ee = 100%[α]D25=+20.0 (c 1.7, CHCl3)source of chirality: (S)-2-butan-1-olAbsolute configuration: (S)

(2E,4S)-2,4-Dimethyl-2-hexen-1-olC8H16OEe = 100%[α]D25=+22.5 (c 1.3, CHCl3)source of chirality: (S)-2-butan-1-olAbsolute configuration: (S)

(2E,4S)-2,4-Dimethyl-2-hexenyltriphenylphosphonium bromideC32H30BrPEe = 100%[α]D25=+12.4 (c 0.5, CHCl3)source of chirality: (S)-2-butan-1-olAbsolute configuration: (S)

Diethyl (2R,3R)-1,4-dioxaspiro[4,4]nonane-2,3-dicarboxylateC13H20O6Ee = 100%[α]D25=-32.5 (c 3.4, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3R)

Diethyl (2R,3R)-2-methyl-1,4-dioxaspiro[4,4]nonane-2,3-dicarboxylateC14H22O6Ee = 100%[α]D25=-56.1 (c 1.75, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3R)

Diethyl (2R,3S)-2-methyl-1,4-dioxaspiro[4,4]nonane-2,3-dicarboxylateC14H22O6Ee = 100%[α]D25=-24.4 (c 0.7, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3S)

Ethyl (2R,3S)-3-[(1Z,3E,5S)-3,5-dimethylhepta-1,3-dienyl]-2-methyl-1,4-dioxaspiro[4.4]nonane-2-carboxylateC20H32O4Ee = 100%[α]D25=+15.9 (c 1.1, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3S,5′S)

Ethyl (2R,3R)-3-[(1Z,3E,5S)-3,5-dimethylhepta-1,3-dienyl]-2-methyl-1,4-dioxaspiro[4.4]nonane-2-carboxylateC20H32O4Ee = 100%[α]D25=+18.9 (c 1.0, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3R,5′S)

Ethyl (2S,3R)-3-[(1Z,3E,5S)-3,5-dimethylhepta-1,3-dienyl]-2-methyl-1,4-dioxaspiro[4.4]nonane-2-carboxylateC20H32O4Ee = 100%[α]D25=+28.0 (c 1.1, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2S,3R,5′S)

Ethyl (2S,3S)-3-[(1Z,3E,5S)-3,5-dimethylhepta-1,3-dienyl]-2-methyl-1,4-dioxaspiro[4.4]nonane-2-carboxylateC20H32O4Ee = 100%[α]D25=+13.7 (c 1.1, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2S,3S,5′S)

Ethyl (2R,3S,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienylcarboxylateC15H26O4Ee = 100%[α]D25=-80.1 (c 1.0, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3S,8S)

Ethyl (2R,3R,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienylcarboxylateC15H26O4Ee = 100%[α]D25=+44.7 (c 1.1, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3R,8S)

Ethyl (2S,3R,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienylcarboxylateC15H26O4Ee = 100%[α]D25=+110.4 (c 1.0, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2S,3R,8S)

Ethyl (2S,3S,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienylcarboxylateC15H26O4Ee = 100%[α]D25=+3.4 (c 1.25, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2S,3S,8S)

Methyl N-[(2R,3S,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienoyl]glycinateC16H27NO5Ee = 100%[α]D25=-16.8 (c 2.5, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3S,8S)

Methyl N-[(2R,3R,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienoyl]glycinateC16H27NO5Ee = 100%[α]D25=+38.5 (c 3.75, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2R,3R,8S)

Methyl N-[(2S,3R,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienoyl]glycinateC16H27NO5Ee = 100%[α]D25=+55.0 (c 1.0, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2S,3R,8S)

Methyl N-[(2S,3S,4Z,6E,8S)-2,3-dihydroxy-2,6,8-trimethyldeca-4,6-dienoyl]glycinateC16H27NO5Ee = 100%[α]D25=-3.2 (c 2.5, CHCl3)source of chirality: (+)-diethyl-l-tartrateAbsolute configuration: (2S,3S,8S)