6-Lactones racemic mixtures

Figure 3.7 [continued) (b) Chromatograms of (iii) the dichloromethane extract of strawberry fruit yoghurt analysed with an apolar primary column, with the heart-cut regions indicated, and (iv) a non-racemic mixture of y-deca-(Cio) and 7-dodeca-Cj2 lactones isolated by heart-cut transfer, and separated by using a chiral selective modified cyclodextrin column. Reproduced from A. Mosandl, et al J. High Resol. Chromatogr. 1989, 12, 532 (39f. 

When the natural product source contains racemic mixtures (of isomeric forms), then clearly the assignment of signal value to either or both variants of a compound needs to be determined. Alterations in receptor detection of chirality can change sensitivity to the geometrically alternate compound over the range 101 to 106. Of the lactones passed into urine and deposited on tarsal hairs of Black-tailed deer (Odocoileus... 

D-Pantolactone and L-pantolactone are used as chiral intermediates in chemical synthesis, whereas pantoic acid is used as a vitamin B2 complex. All can be obtained from racemic mixtures by consecutive enzymatic hydrolysis and extraction. Subsequently, the desired hydrolysed enantiomer is lactonized, extracted and crystallized (Figure 4.6). The nondesired enantiomer is reracemized and recycled into the plug-flow reactor [33,34]. Herewith, a conversion of 90-95% is reached, meaning that the resolution of racemic mixtures is an alternative to a possible chiral synthesis. The applied y-lactonase from Fusarium oxysporum in the form of resting whole cells immobilized in calcium alginate beads retains more than 90% of its initial activity even after 180 days of continuous use. The biotransformation yielding D-pantolactone in a fixed-bed reactor skips several steps here that are necessary in the chemical resolution. Hence, the illustrated process carried out by Fuji Chemical Industries Co., Ltd is an elegant way for resolution of racemic mixtures. 

Dipolar cycloadditions of nitrone (614) to a,P-unsaturated 8-lactones, such as nonchiral D7a, racemic mixture D7c/D7d, enantiopure D-glycero D7c, and... 

Carbonylative kinetic resolution of a racemic mixture of trans-2,3-epoxybutane was also investigated by using the enantiomerically pure cobalt complex [(J ,J )-salcy]Al(thf)2 [Co(CO)4] (4) [28]. The carbonylation of the substrate at 30 °C for 4h (49% conversion) gave the corresponding cis-/3-lactone in 44% enantiomeric excess, and the relative ratio (kre ) of the rate constants for the consumption of the two enantiomers was estimated to be 3.8, whereas at 0 °C, kte = 4.1 (Scheme 6). This successful kinetic resolution reaction supports the proposed mechanism where cationic chiral Lewis acid coordinates and activates an epoxide. 

A lactone, (2 )-9-octadecen-4-olide, has been identified as a female specific antennally active compound from the currant stem girdler, Janus integer Norton (Hymenoptera Cephidae). Comparison of the y-lactone and a synthesized racemic mixture of (2 )-9-octadecen-4-olide on a chiral GC column showed the presence of a single component in the natural material. ... 

Many of these substituted lactones possess at least one chiral center and are thus present as a mixture of stereoisomers. The simplest case is based on the polymerization of lactones with one chiral center, which is thus a mixture of two R and S enantiomers. These stereochemical aspects have been completely overlooked in many works the polymerization is carried out on a racemic mixture and no stereo selectivity is reported or even discussed. It is worth pointing out that several metal-based catalysts were successfully designed for the stereoselective polymerization of... 

Interestingly, enzymes are chiral catalysts and their potential for enantio-selective polymerization has been investigated [93]. Several examples are reported where a racemic mixture of lactones is polymerized by enzymatic polymerization to afford the corresponding optically active polyester [93]. For instance, lipase CA (Novozym 435) catalyses the ROP of racemic 4-methyl-s-caprolactone and 4-ethyl-s-caprolactone in bulk at 45 °C and 60 °C to afford (S )-eiuiched poly(4-methyl-e-caprolactone) and poly(4-ethyl- -caprolactone) with an enantiomeric purity higher than 95% [153]. 

Neonepetalactone, 61 (Fig. 1.2.3), a bioactive compound found to be quite attractive to cats [41], was isolated in 1965 from the leaves and galls of Actinidia polygama by T. Sakan et al. and its absolute configuration was determined in 1980 [41b]. As some syntheses of the racemic mixture or ex-chiral-pool syntheses had already been reported, we realized that our SAMP/RAMP hydrazone methodology would make it possible to develop a very short asymmetric synthesis of this bioactive 8-lactone. 

Viridifloric /3-lactone, 143, has been identified as one of the pheromone components of a complex mixture of volatiles released by the pheromone glands of the male Idea leuconoe butterfly during courtship <1996BMC341>. A racemic mixture of both diastereoisomers was synthesized in four steps from the dilithio salt of 3-methylbutyric acid 144 alkylation with ethanal, dehydration of the secondary alcohol with phosphorus pentoxide, dihydroxylation of the C-C double bond with osmium tetraoxide, and finally formation of the /3-lactone by cyclization with sulfonyl chloride. By comparison with the sample isolated from I. leuconoe, the absolute configuration was established to be (2V,3V)-2-hydroxy-2-(l-methylethyl)-3-butanolide 143. 

Figure 19.2. Enantioselective hydrolysis of D-panotyl lactone in a racemic mixture by oxysporum.

All the foregoing syntheses of 0,0,0-orthoesters required at least two steps because 0,0,0-orthoesters cannot usually be prepared directly from esters by reaction with alcohols under add conditions analogous to the preparation of acetals from aldehydes and ketones. There are some exceptions.237 -239 For example. reaction of the racemic mixture of cis- and fraftf-lactones in Scheme 2.115 with (/ ,/ )-butane-2,3-diol in refluxing benzene afforded a mixture of four diastereoisomeric orthoesters (99%) in the ratio 6 6 1 1 that could be sepa-... 

Intraperitoneal injection of 35-butylphthalide (32) protected both mice and rats against seizure development induced by audio- and electro-shock, and convulsive agents such as metrazole or coriaria lactone [292-295]. However, controversial results were obtained in a separate study reported by Dong and co-workers [296]. In their murine model, subcutaneous administration the / -enantiomer 31 and its racemic mixture... 

We found in our laboratory, a novel lactonohydrolase that catalyzes reversible hydrolysis of various lactones including aldonate lactones and aromatic lactones. The enzyme was crystallized from Fusarium oxysporum and characterized. It has been shown that the enzyme hydrolyzes only D-pantoyl lactone, a chiral intermediate for the commercial production of D-pantothenate, in a racemic mixture of pantoyl lactone and that the enzyme is very useful for the optical resolution of racemic pantoyl lactone (Fig. 3)7. When F. oxysporum mycelia entrapped in calcium alginate gel were incubated in 30% solution of DL-pantoyl lactone, almost stoichiometric hydrolysis of D-pantoyl lactone was observed. After repeated reactions for 150 times over 150 days, the mycelia retained more than 90% of their initial activity. A 1,000... 

In this communication we report a study of the stereochemical features of this catalytic process and the use of chiral diphosphine modified catalysts for the enantioselective synthesis of certain naturally ocurring lactones through kinetic resolution of a racemic mixture of the starting ketones. 

Optically pure a-hydrojq -y-lactones. The a-hydro gr-y-lactones obtained by Lubineau were racemic mixtures many groups have worked in the aim to develop an asymmetric version of the synthesis or to develop efficient methods for their resolution. Most of the time, the syntheses used the enzymatic resolution described by Roberts in 1994. Thus ot-hydro)y-y-lactones could be resolved by an enantioselective acetylation using Candida cylindracea lipase or Pseudomonas Fluorescens lipase. In a large scale (>2kg), the enzymatic hydrolysis of the racemic butyrate ester was preferred because the reaction is faster and leads to a purer compound with a best yield (Scheme 6). 

Unlike enzymatic reactions, microorganisms have the ability to perform multiple reactions, and they do not require cofacors for regeneration (albeit they require nutrients). They may be used to generate a flavor compound from a nonvolatile precursor (e.g., produce a lactone from castor oil), to effect the bioconversion of one volatile to another (e.g., valencene to nootkatone), or effect a chiral resolution (a racemic mixture of menthol). The primary limitation of using microoganisms for... 

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

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