Sophorolipid lactone

Scheme 89 Total synthesis of sophorolipid lactone 449 by sequential RCAM and -selective partial hydrogenation [186]...

Sophorolipid lactone (34) was obtained from an open-chain bisalkyne precursor (concomitant formation of 2-butyne) in a macrocyclization yield of 78% [29], The epothilones have been obtained through non-stereoselective alkene metathesis [26d], making them worthwhile targets for the combination alkyne metathesis/Lindlar hydrogenation to assemble the C12-C13 Z double bond. Furthermore, epothilone C (35) shows the most complex array of functional groups among the substrates of alkyne metathesis. The macrocyclization yield, starting from the expected OTBS-protected precursor (not shown) was 81% [23, 30]. Neither... 

Furstner, A., Radkowski, K., Grabowski, J., Wirtz, C., Mynott, R. Ring-Closing Alkyne Metathesis. Application to the Total Synthesis of Sophorolipid Lactone. J. Org. Chem. 2000, 65, 8758-8762. 

The synthesis of sophorolipid lactone 28 demonstrated the low Lewis acidity of the metal center in 3 and the resulting catalytically active species. A high yield of 26 was achieved in RCAM of diyne 25 despite the presence of acid-labile PMB ethers and glycidic linkages (Scheme 7.11) [35]. Once again, stereoselective semi-reduction resulted in quantitative yield of the required (Z)-olefin 27. 

Figure 7.5. Sophorolipid (17-L-(. 2 -0-P-glucopyranosyl-P-D-glucopyranosyl]-oxy)-9-cis-octadecenoic acid T,4"-lactone 6, 6"-diacetate (A) and its free-acid form (B).

Among the 24-membered lactones, one derived from natural sophorolipid was polymerised via lipase-catalysed ROP to form a glycolipid-based polyester [118]. 

Lactonic sophorolipids exhibit antimicrobial activity and degree of antimicrobial activity is related to the structure of sophorolipids, which is determined by the type of carbon source used for fermentation." Sophorolipids derivatives such as sophorolipids diacetate ethyl ester derivatives have been reported as having spermicidal and virucidal activity and can be used in preparation of microbicidal contraceptions." Administration of sophorolipids reduces the mortality associated with septic shock in rats due their immunomodulatory function." Sophorolipids capped silver nanoparticles are very stable and show strong antimicrobial activity against gram-positive and gram-negative bacteria." ... 

Well-defined sophorolipid biosurfactant analogs were also prepared via enzymatic synthesis for the evaluation of the bioactivity and as building blocks for the preparation of glycolipid-based polymers [107]. The direct enzymatic ring-opening polymerization of lactone sophorolipids (SLs) was carried out with lipases. The reaction proceeded with the formation of mono-acylated lactone SLs and the subsequent conversion of the intermediates to oligomers and polymers (Scheme 12) [108]. 

The acidic form of classical sophorolipid (a deacetylated compound) produced by alkaline hydrolysis of the native lactonic form (Fig. 2) was successfully converted by enzymatic biotransformation (glycosidase catalysis) to an acidic glucose lipid [44]. Another modification was performed with alkyl-amines leading to alkylamides of the acidic sophorolipid [123]. Bisht et al. [128] reported an efficient chemoenzymatic route that led to an 6-O-acryloyl-sophorolipid macrolactone analog. The homopolymerization of this monomer as well as its copolymerization with acrylic acid and acrylamide led in maximum to a molecular weight of 4.2 x 10" Da. The first total synthesis of a major component of the microbial classical lactonic sophorolipid was described by Fiirstner et al. [129]. 

Sophorolipids possessing lactone rings are generally more lipophilic than rhanmoUpids and are less sensitive to pH, and often have a lower surface activity per mass than rhamnolipids. They are typically obtained from bacteria or yeasts, particularly from Candida sp. Fermentation is often conducted under nitrogen starvation conditions, with abundant dissolved oxygen being present (Pinzon et al., 2009). Sophorolipids can undergo chemical or enzymatic modification to further tune their surface-active properties (Ashby et al, 2009). 

Native sophorolipids are understood to be produced by the wild-type organism and contain a C16-C18 hydroxy fatty acid. Two types of variations occur the nature of the lipophilic moiety and the amount of esterification. For the lipophilic moiety, predominantly hydroxy stearic acid is observed in the case of de novo synthesis [23] and when feeding a fatty acid of a suitable length, the concurrent hydroxy fatty acid is found. The extent of the esterification, either acetylation or lactonization, determines the solubility of the final product and is influenced by the pH. A value of 3-3.5 predominantly yields the poorly soluble diacetyl lactone and biosynthesis using a pH of 2 results in a more soluble and thus less esterified product. It is this last parameter that most influences the emulsifying properties of the sophorolipids. Adapting these properties to specific applications is further explored in Section 11.2. 

Diacetylated lactonic sophorolipids have both esteric and glycosidic bonds which exhibit different sensitivities to either acid or alkaline hydrolysis. The latter will only hydrolyse the esters whereas acid hydrolysis at first cleaves the esters and, under more harsh reaction conditions, removes the sophorose moiety to yield a hydroxy fatty acid. In performing alkaline hydrolysis, the gradual removal of the esters transforms the solid... 

Figure 11.6 Alkaline (first step) and acid (both steps) hydrolysis of a diacetylated lactonic sophorolipid.

Treatment of the diacetylated lactonic sophorolipid with an alcohol will result in removing both acetyl groups and opening the lactone ring to the concurrent alcohol ester. Figure 11.8 depicts the transesterification of a sophorolipid with methanol. 

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