Biosynthesis of lactones from diols mediated by an artificial flavin

Background Lactones are important compounds in the field of medicine, material and chemical industry. One of the promising accesses to these flexible scaffolds is NAD(P)+-dependent alcohol dehydrogenases-catalyzed oxidative lactonization of diols, which relies on the construction of an efficient NAD(P)+ regeneration system. Results In this study, a novel system combining horse liver alcohol dehydrogenase (HLADH) with the synthetic bridged flavin cofactor was established for biosynthesis of lactones. The reaction conditions of this system were optimized and a variety of lactones including chiral lactones were efficiently obtained from various diols. Compared to the previously reported NAD(P)+-regeneration systems, this system showed better regeneration efficiency and product yield. A two-phase system was further applied to solve the problem of product inhibition, and 80% yield was obtained at the condition of 300 mM substrate. Conclusions This study provides an efficient method to synthesis of lactones from diols under mild conditions. We believe this system will be a promising alternative to promote the synthesis of other valuable compounds. Graphic abstract

Biosynthesis of Lactones From Diols Mediated by an Artificial Flavin

Background: Lactones are important compounds in the field of medicine, material and chemical industry. One of the promising accesses to these flexible scaffolds is NAD(P)+-dependent alcohol dehydrogenases-catalyzed oxidative lactonization of diols, which relies on the construction of an efficient NAD(P)+ regeneration system. Results: In this study, a novel system combining horse liver alcohol dehydrogenase (HLADH) with the synthetic bridged flavin cofactor was established for biosynthesis of lactones. The reaction conditions of this system were optimized and a variety of lactones including chiral lactones were efficiently obtained from various diols. Compared to the previously reported NAD(P)+-regeneration systems, this system showed better regeneration efficiency and product yield. A two-phase system was further applied to solve the problem of product inhibition, and 80% yield was obtained at the condition of 300 mM substrate.Conclusions: This study provides an efficient method to synthesis of lactones from diols under mild conditions. We believe this system will be a promising alternative to promote the synthesis of other valuable compounds.

Efficient asymmetric syntheses of α-quaternary lactones and esters through chiral bifunctional sulfide-catalyzed desymmetrizing bromolactonization of α,α-diallyl carboxylic acids

Asymmetric halolactonizations are powerful methods for the syntheses of chiral lactones. Catalytic and highly enantioselective halolactonizations of α-allyl carboxylic acids, however, continue to present a formidable challenge. Herein, we report...

Evaluation of fungicidal, bactericidal and anti-tumor activities of lactones of medium and large sizes of cycles obtained from levoglucosenone

Medium and large lactones attract the attention of chemists by the uniqueness of their structure, versatile biological activity and limited availability. Among the secondary metabolites of this group, β-lactones are more common, then γ- and δ-lactones, classical and non-classical macrolides, polyene antibiotics, spiro-macrolides and macrolactones. On the basis of many lactones, important preparations of the most diverse pharmacological action have been obtained. Earlier, we proposed a 3-stage scheme for the synthesis of chiral lactones of medium and large size based on levoglucosenone. The lactones obtained according to this scheme contain the carbohydrate residue annelated at the ,γ -positions relative to the hydroxy group. To study the structure-activity relationship, it is necessary to establish the biological role of this carbohydrate residue in reference lactones. For this purpose, a number of lactones were obtained on the basis of levoglucosenone and their in vitro bioscreening of antifungal, antimicrobial, and antitumor activity was performed. It was found that the methyl substituent in the ω-position in the lactone and the benzene ring annulated with the lactone cycle exhibit a slight fungistatic activity towards the fungi: Bipolaris sorokiniana, Fusarium oxysporum, Rhizoctonia solani. Macrocyclic lactone and lactone annelated benzene ring showed weak cytotoxic properties against cells of LOX IMVI (melanoma) and A498, UO-31 (kidney cancer).

Catalytic Asymmetric Synthesis of Geminal-Dicarboxylates

<p>Stereogenic acetals, spiroacetals and ketals are well-studied stereochemical features that bear two heteroatoms at a common carbon atom. These stereocenters are normally found in cyclic structures while linear (or acyclic) analogues bearing two heteroatoms are rare. Chiral geminal-dicarboxylates are illustrative, there is no current way to access this class of compounds while controlling the stereochemistry at the carbon center bound to two oxygen atoms. Here we report a rhodium-catalyzed asymmetric carboxylation of ester-containing allylic bromides to form stereogenic carbon centers bearing two different carboxylates with high yields and enantioselectivities. The products, which are surprisingly stable to a variety of acidic and basic conditions, can be manipulated with no loss of enantiomeric purity as demonstrated be ring closing metathesis reactions to form chiral lactones, which have been extensively used as building blocks in asymmetric synthesis.<br></p>