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Total synthesis of the putative structure of the proposed Banyasin A.

Gao X, Ren Q, Choi S, Xu Z, Ye T - Front Chem (2015)

Bottom Line: The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described.The structure synthesized appears to be different from that of the natural product.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen, China.

ABSTRACT
The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described. The structure synthesized appears to be different from that of the natural product.

No MeSH data available.


Revised route for the synthesis of 3-amino-2-methyl-5E-octenoic acid 4.
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Figure 5: Revised route for the synthesis of 3-amino-2-methyl-5E-octenoic acid 4.

Mentions: The synthesis commenced from crotylation of 3-benzyloxy-propionaldehyde (9) with Brown's (E)-(+)-crotyldiisopinocampheylborane, prepared from (+)-diisopinocampheyl(methoxy)borane, and yielded the anti-homoallylic alcohol 10 as a single diastereomer after silica gel chromatography (Figure 4). (Brown and Bhat, 1986) The homoallylic alcohol was then converted to its mesylate derivative, followed by exposure of the resulting mesylate to sodium azide in DMF furnished, with inversion of configuration, the corresponding azido derivative 11 in 59% overall yield from aldehyde 9. The azide moiety of 11 was reduced by the action of triphenylphosphine to afford the corresponding primary amine, which was then protected as a Boc carbamate (12) in 94% yield over two steps. Oxidative cleavage of the olefin of 12 using OsO4–NaIO4 in the presence of 2,6-lutidine afforded an aldehyde, which was further oxidized to the corresponding carboxylic acid by Pinnick oxidation. A subsequent methylation of the carboxylic group using iodomethane and potassium carbonate gave the methyl ester 13 in 72% yield over the three steps. Subsequent removal of the benzyl ether under hydrogenative conditions followed by Dess-Martin oxidation of the resultant primary alcohol gave rise to aldehyde 14 in 79% yield. The Kocienski-modified Julia olefination of aldehyde 14 with sulfone 15 in THF at −78°C delivered olefin 16 as an inseparable mixture of olefin isomers (4:1) in favor of the desired E configuration. (Blakemore et al., 1998). Subsequent saponification of the methyl ester gave 3-amino-2-methyl-5E-octenoic acid 4a in 97% yield. Further incorporation of 4a in the construction of the macrocycle reveled the undesired geometrical isomer could not be completely removed in the later stage of the synthesis. Bearing in mind the problems encountered with the formation of an inseparable mixture of olefin isomers, we required an alternative approach which could efficiently deliver 3-amino-2-methyl-5E-octenoic acid 4 in fairly high purity. Thus, the homoallylic alcohol 10 was protected as its tert-butyldimethylsilyl ether and the terminal alkene underwent a substrate-controlled dihydroxylation in the presence of osmium tetroxide to provide 18 as a diastereomeric mixture (3.7:1) of diols in 88% combined yields (Figure 5). This mixture was simply exposed to 2,2-dimethoxypropane under acidic conditions to furnish the corresponding acetonide, which was then subjected to hydrogenolysis of the benzyl ether to give rise to 19 in 86% yield for two steps. Dess-Martin oxidation of 19 provided crude aldehyde, which was treated with the anion derived from sulfone 15 and KHMDS. When the olefination was performed in 1,2-dimethoxyethane (DME) at −68°C, we obtained E/Z mixtures (13/1) of olefins 20 in 83% yield. Removal of the TBS group in 20 using TBAF and the resultant secondary hydroxy group engaged in Mitsunobu reactions using diphenylphosphoryl azide (DPPA) (Lal et al., 1977) as the nucleophile to give rise to azide 21 in 78% yield. Acid-catalyzed deprotection of the acetonide functionality of 21, followed by oxidative cleavage of the resulting diol with sodium periodate, followed by Pinnick oxidation (Bal et al., 1981) afforded the carboxylic acid 22a in 79% yield over three steps. As the absolute configuration of two stereogenic centers in the subunit 4 was not assigned in the original isolation work, our synthetic strategy grew from the desire to have a versatile approach to make all four possible diastereomers of 4, along with the defined stereochemistry of the disubstituted olefin component. With a practical route to 22a in hand, we synthesized the other three possible diastereomers (22b, 22c, and 22d) through the condensation of aldehyde 9 with Brown's (E)-(−)-crotyldiisopinocampheylborane, (Z)-(+)-crotyldiisopinocampheylborane and (Z)-(−)-crotyldiisopinocampheylborane, respectively. Azido acid 22a was then subjected to hydrogenation in the presence of the palladium on charcoal and the resulting amine was protected as its tert-butoxycarbonyl carbamate 4a.


Total synthesis of the putative structure of the proposed Banyasin A.

Gao X, Ren Q, Choi S, Xu Z, Ye T - Front Chem (2015)

Revised route for the synthesis of 3-amino-2-methyl-5E-octenoic acid 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362330&req=5

Figure 5: Revised route for the synthesis of 3-amino-2-methyl-5E-octenoic acid 4.
Mentions: The synthesis commenced from crotylation of 3-benzyloxy-propionaldehyde (9) with Brown's (E)-(+)-crotyldiisopinocampheylborane, prepared from (+)-diisopinocampheyl(methoxy)borane, and yielded the anti-homoallylic alcohol 10 as a single diastereomer after silica gel chromatography (Figure 4). (Brown and Bhat, 1986) The homoallylic alcohol was then converted to its mesylate derivative, followed by exposure of the resulting mesylate to sodium azide in DMF furnished, with inversion of configuration, the corresponding azido derivative 11 in 59% overall yield from aldehyde 9. The azide moiety of 11 was reduced by the action of triphenylphosphine to afford the corresponding primary amine, which was then protected as a Boc carbamate (12) in 94% yield over two steps. Oxidative cleavage of the olefin of 12 using OsO4–NaIO4 in the presence of 2,6-lutidine afforded an aldehyde, which was further oxidized to the corresponding carboxylic acid by Pinnick oxidation. A subsequent methylation of the carboxylic group using iodomethane and potassium carbonate gave the methyl ester 13 in 72% yield over the three steps. Subsequent removal of the benzyl ether under hydrogenative conditions followed by Dess-Martin oxidation of the resultant primary alcohol gave rise to aldehyde 14 in 79% yield. The Kocienski-modified Julia olefination of aldehyde 14 with sulfone 15 in THF at −78°C delivered olefin 16 as an inseparable mixture of olefin isomers (4:1) in favor of the desired E configuration. (Blakemore et al., 1998). Subsequent saponification of the methyl ester gave 3-amino-2-methyl-5E-octenoic acid 4a in 97% yield. Further incorporation of 4a in the construction of the macrocycle reveled the undesired geometrical isomer could not be completely removed in the later stage of the synthesis. Bearing in mind the problems encountered with the formation of an inseparable mixture of olefin isomers, we required an alternative approach which could efficiently deliver 3-amino-2-methyl-5E-octenoic acid 4 in fairly high purity. Thus, the homoallylic alcohol 10 was protected as its tert-butyldimethylsilyl ether and the terminal alkene underwent a substrate-controlled dihydroxylation in the presence of osmium tetroxide to provide 18 as a diastereomeric mixture (3.7:1) of diols in 88% combined yields (Figure 5). This mixture was simply exposed to 2,2-dimethoxypropane under acidic conditions to furnish the corresponding acetonide, which was then subjected to hydrogenolysis of the benzyl ether to give rise to 19 in 86% yield for two steps. Dess-Martin oxidation of 19 provided crude aldehyde, which was treated with the anion derived from sulfone 15 and KHMDS. When the olefination was performed in 1,2-dimethoxyethane (DME) at −68°C, we obtained E/Z mixtures (13/1) of olefins 20 in 83% yield. Removal of the TBS group in 20 using TBAF and the resultant secondary hydroxy group engaged in Mitsunobu reactions using diphenylphosphoryl azide (DPPA) (Lal et al., 1977) as the nucleophile to give rise to azide 21 in 78% yield. Acid-catalyzed deprotection of the acetonide functionality of 21, followed by oxidative cleavage of the resulting diol with sodium periodate, followed by Pinnick oxidation (Bal et al., 1981) afforded the carboxylic acid 22a in 79% yield over three steps. As the absolute configuration of two stereogenic centers in the subunit 4 was not assigned in the original isolation work, our synthetic strategy grew from the desire to have a versatile approach to make all four possible diastereomers of 4, along with the defined stereochemistry of the disubstituted olefin component. With a practical route to 22a in hand, we synthesized the other three possible diastereomers (22b, 22c, and 22d) through the condensation of aldehyde 9 with Brown's (E)-(−)-crotyldiisopinocampheylborane, (Z)-(+)-crotyldiisopinocampheylborane and (Z)-(−)-crotyldiisopinocampheylborane, respectively. Azido acid 22a was then subjected to hydrogenation in the presence of the palladium on charcoal and the resulting amine was protected as its tert-butoxycarbonyl carbamate 4a.

Bottom Line: The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described.The structure synthesized appears to be different from that of the natural product.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen, China.

ABSTRACT
The first total synthesis of four possible isomers of a molecule possessing the configuration proposed for Banyasin A is described. The structure synthesized appears to be different from that of the natural product.

No MeSH data available.