2-hydroxyhexanoate

In order to develop a tissue-engineered heart valve, a group at Children s Hospital in Boston evaluated several synthetic absorbable polyesters as potential scaffolding materials for heart valves. Unfoitu-nately, the most synthetic polyesters proved to be too stiff to be function as flexible leaflets inside a tri-leaflet valve. " In the late 1990s, a much more flexible PHAs called poly-3-hydroxyoctanoate-co-3-hydroxyhexanoate (PHO) was used as the scaffold material for the valve leaflet, and then the entire heart valve. ... 

There is considerable interest in synthesizing copolymers. This is actually possible if organisms are confronted with mixtures of so-called related and unrelated substrates. Copolymers can also be synthesized from unrelated substrates, e.g., from glucose and gluconate. The 3-hydroxydecanoate involved in the polyester is formed by diversion of intermediates from de novo fatty-acid synthesis [41,42]. Related , in this context, refers to substrates for which the monomer in the polymer is always of equal carbon chain length to that of the substrate offered. Starting from related substrates, the synthesis pathway is closely connected to the fatty-acid /1-oxidation cycle [43]. In Pseudomonas oleovor-ans, for example, cultivated on octane, octanol, or octanoic acid, the synthesized medium chain length polyester consists of a major fraction of 3-hydroxyoc-tanoic acid and a minor fraction of 3-hydroxyhexanoic acid. If P. oleovorans is cultivated on nonane, nonanol, or nonanoic acid, the accumulated polyester comprises mainly of 3-hydroxynonanoate [44]. 

C4 = 3-hydroxybutyric acid, C5 = 3-hydroxyvaleric acid, C6 = 3-hydroxyhexanoic acid, C7 = 3-hydroxyheptanoic acid, C8 = 3-hydroxyoctanoic acid, C9 = 3-hydroxynonanoic acid CIO = 3-hydroxydecanoic acid. 

All purified poly(HA) depolymerases are specific for either poly(HASCL) or poly(HAMCL). Even a poly(3HB) depolymerase of S. exfoliatus K10, a strain that degrades both poly(3HB) and poly(3HO), is specific for poly(HASCL) [49]) indicating at least one additional depolymerase with specificity for poly(HAMCL) in S. exfoliatus. Experiments with copolymers consisting of 3-hydroxybutyrate and 3-hydroxyhexanoate and A.faecalis T1 poly(3HB) depolymerase are in agreement with the results obtained with poly(HASCL) and poly(HAMCL) the depolymerase was not able to hydrolyze ester bonds between two 3HAMCL monomers and between 3-hydroxybutyrate and 3-hydroxyhexanoate [50]. 

Injectable liquid polyhydroxyalkanoate compositions consisting of the transesterification product of poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate) with 1,3-butanediol were prepared by Williams et al. (3) and used in soft tissue repair, augmentation, and viscosupplementation in humans. 

Bornscheuer et al. (1992) Batch Esterification, hydrolysis, and transesterification of 3-hydroxyhexanoic acid methylester Lipase from Pseudomonas cepacia... 

Ethyl butanoate, 2-methyl-3-buten-2-ol (111), ethyl acetate, ethyl 3-hydroxyhexanoate (112),... 

Procter Gamble is the other leading pioneer on the field of PHA biodegradable polymers. The Nodax biopolymers are based on the copolymer PHBH, a copolymer polyester of 3-hydroxybutyric and 3-hydroxyhexanoic acid. The higher the 3-hydroxyhexanoic acid comonomer component, the more flexible... 

PHBH poly(3-hydroxybutyric acid-co-3-hydroxyhexanoic acid)... 

As shown in Figure 7 ethyl 3-hydroxyhexanoate, isolated from purple passion fruit possessed the (R)-configuration, comparable to the hydroxyacid ester obtained by the reduction with baker s yeast. In contrary to that methyl 3-hydroxyhexanoate, which was isolated from aroma extracts of pineapple, consisted of the (S)-enantiomer (91 %). ... 

Capillary gas chromatographic investigation of diastereoisomeric derivatives revealed that in analogy to results obtained without precursors the chiral metabolites are present as mixtures of enantiomers. However for only a few of these compounds the ratios of enantiomers are identical with those determined in pineapple without precursors. The enantiomeric compositions of ethyl 3-hydroxyhexanoate and ethyl 3-acetoxyhexanoate are almost opposite to those determined for the naturally occurring methyl esters. 6-Octalactone obtained after addition of 5-oxooctanoic acid to pineapple tissue is almost optically pure (92% S) on the other hand -octalactone is naturally present in pineapple tissue as nearly racemic mixture (Table 1,8). 

Figure 1 shows part of a reconstructed ion chromatogram of a pineapple aroma extract isolated after incubation of pineapple slices with 3-hydroxyhexanoic acid-3-di. GC-MS detection of deuterated compounds showed that the following pathways are active (a) esterification leading to methyl and ethyl esters, (b) dehydration to (E)-2-and (E)-3-hexenoates, and (c) chain elongation to methyl 5-hydroxy octanoate followed by acetylation (methyl 5-acetoxyoctanoate) and cyclization ( 6-octalactone). 

Figure 1. Part of a capillary gas chronatogram (reconstructed ion detection) of an aroma extract of pineapple tissue, isolated after addition of 3-hydroxyhexanoic acid-3-di (CP Wax 52 CB column,...

Figure VIII shows the enantiomeric composition of various hydroxy- and acetoxyacid esters and of if -hexa-and -octalactone isolated from pineapple. Methyl 3-hydroxyhexanoate and methyl 3-acetoxyhexanoate are mainly of the (S)-configuration corresponding to intermediates of B-oxidation. The optical purity of the 5-acetoxy esters is lower than of the 3-acetoxy derivatives. The lactones were mainly of the (R)-configuration. Figure IX presents a possible pathway to explain the formation of these compounds. Methyl (S)-(+)-3-hydroxyhexanoate and methyl (S)-3-acetoxyhexanoate may be derived from (S)-3-hydroxyhexanoyl-CoA by transacylation with methanol and acetyl-CoA, respectively. The biosynthesis of 5-hydroxyacids is still unknown, but they may be formed by elongation of 3-hydroxyacids with malonyl-ACP. This hypothesis could explain their varying enantiomeric composition relative to the 3-hydroxyacids. However, hydration of unsaturated acids and/or the reduction of 5-oxoacids may be involved.

Figure VIII. Capillary GC-separation of the (R)-(+)-PEIC-derivatives of chiral (main) constituents isolated from pineapple. 3-Hydroxyhexanoate and 3-aeetoxyhexanoate were separated as the (R)-(+)-MTPA-derivatives.

Figure X. Possible pathway for the biosynthesis of (Z)-3-hexanoic acid esters, (Z)-3-hexanol, (Z)-3-hexenyl esters, 3-hydroxyhexanoic acid esters, and sulfur-containing components in passion fruit.

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