A Short Review on Chiral Alcohols Verses Bio-Catalysis

Catalyst is a chemical molecule or metal substance which enhances the rate of reaction is called catalyst, the catalyst present in the living organisms to carryout biochemical reactions or metabolic pathways. Exames oxidoreductases, lyases, ligages, proteases, hydrolases, esterases, pectinases etc. are Different methodologies available in synthesis of chiral molecules chemical/biocatalysis. The enormous potential of biocatalysts (microorganisms and enzymes) in synthesis of chiral molecules in mild conditions (pH and temperate) with high chemo-, regio-, enantio and functional selectivity with decrease formation of by-products, with short reaction steps (reactions which are not easily conducted classical organic reactions) (Long chemical processes with tedious blocking and de-blocking steps). Thus the use of biocatalyst has attracted a great attention from the green chemistry perspective (expensive chiral reagents/ environmentally hazardous heavy metals). Biocatalysts are well known for their enzymatic activity towards numerous reactions ranging from in-vivo living cells (biochemical pathways) to in-vitro chemical reactions (reduction and transesterification) with enantiomeric purity and specificity. In this review the discussion is about synthesis of chiral using different kinds of biocatalysts. Daucus Carota, Pisum Sativa, Novazyme P-435, as biocatalysts for chiral alcohols.


Overview of the Chiral Alcohols Verses Bio-catalysis
Life and chirality are strictly connected in carrying out different metabolic functions of the living organism, thus chirality plays an important role in the life of plants and animals. Louis Pasteur (1853) coined the name dissymmetric. Later the term was changed to asymmetry and later it was replaced by the term chirality, a familiar analogy of the mirror image relationship like left and right [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. The chemical complexity is the fundamental from of life and thus the chirality occupies the main features of the living world. Chirality is a phenomenon of geometrical or spatial arrangement of an object which is a non-super imposable mirror image. Chiral molecules that consist of a tetrahedral carbon atom attached to four different groups are called stereo-isomers, and possess identical chemical properties [12][13][14][15][16][17][18][19][20][21][22][23][24][25].
Chiral molecules are widely distributed in nature, and these enantioselective compounds are known to have selective/specific potent biological activities with reduced side effects compared to their racemates [26][27][28][29]. Hence, the synthesis of chiral molecules has drawn immense attention in the pharmaceutical industry as well as by drug regulatory authorities (FDA). A majority of naturally obtained compounds are chiral molecules that are active single isomers. For e.g., between the two enantiomers of Ketamine, S(+) Ketamine is the active anesthetic whereas the other isomer, R(-)Ketamine show undesirable side effects [30][31][32][33][34][35][36][37][38].

Total Synthesis of Some Chiral γ-Lactones
Current discussion highlights the total synthesis of γ-Lactones like the fungicide Paecilocin A, (-)-3-butyl-7-hydroxyphthalide and the insect pheromones (4R)-Dodecanolide and (4R)-Octanolide molecules. Total synthesis of polyketide Paecilocin A which was isolated from the fungus Paecilomyces variotii. This molecule is known to exhibit inhibitory activity against pathogenic bacteria including methicillin-resistant bacteria.
The molecule 3-butyl-7hydroxyphthalide was isolated from a culture broth of Penicillium vulpinum. Furthermore, the lactones are known to function such as hormones, pheromones, and antibiotics [14,[68][69][70][71][72]. Therefore the synthesis of these natural products taken up in an elegant way using lipase mediated kinetic resolution of propargyl alcohol (to create the stereo center of the target molecule) followed by Alder-Rickert reaction (to construct the functionalized aromatic precursor) as the key steps. The synthesis of target molecules, Paecilocin A and (-)-3butyl-7-hydroxyphthalide were accomplished by the transesterification of racemic compounds respectively, which were easily synthesized by alkyne esters and anisole derivative of diene via Alder-Rickert reaction [73]. The optically pure esters were formed from secondary alcohols via the Enzymatic kinetic trans-esterification of racemic propargylic alcohols using Novozym-435 in the presence of vinyl acetate in tert-butyl methyl ether afforded enantioselective (S)acetates. Propargylic alcohols were synthesized from the commercially available aldehydes respectively [74]. In summary, we have successfully demonstrated the enantioselective total synthesis of Paecilocin A & (-)-3-butyl-7-hydroxyphthalide using lipase mediated kinetic resolution of racemic propargyl alcohol and Alder-Rickert reaction. The synthesized chiral molecules possess a potent anti-fungal activity.

Synthesis of (R)-Dodecan-4-olide & (R)-Octan-4-olide Molecules
This Section describes the total synthesis of γ-lactones; optically active 5-and 6-alkyl-substituted (or) γ-and δ-lactones which are important scaffolds in medicinal chemistry and also attractive building blocks in the synthesis of natural products. Lactones contain structural moieties that are frequently present in insect pheromones, cardenolides, lignans and flavor components [16][17][18]. Among various γ-lactones, 4(R)-Dodecanolide is a unique and naturally occurring butanolide; it is isolated from fruits and butterfat. It is a defensive secretion of the pygidial glands of rove beetles, Bledius mandibularis and Bledius spectabilis and is also produced during the bioconversion of soya bean fatty acids by Pencillium roqueforti spores in the presence of an exogenous lipase. These lactones were used as a flavouring agent. The γ-lactones, (4R)-Octanolide is found in strawberry, peach and apricot, it exhibits significant physiological activities [19,75]. The synthesis of target molecules, γ-lactones were accomplished from alkyne esters respectively, which were easily prepared from secondary alcohols via the enzymatic kinetic resolution of racemic propargylic alcohols using Novozym-435 in the presence of vinyl acetate in tertbutyl methyl ether afforded (R)-alcohols. Propargylic alcohols were synthesized from the commercially available aldehydes respectively.

Summary
The current review successfully demonstrated chemo enzymatic total synthesis of wide variety of chiral alcohols such as aromatic and aliphatic chiral alcohols via bio-reduction and synthesis of γ-lactones such as (4R)-Dodecanolide and (4R)-Octanolide using lipase mediated kinetic resolution followed by lactonization as the key steps.