Polyol regioselectivity

In connection with the synthetic work directed towards the total synthesis of polyene macrolide antibiotics -such as amphotericin B (i)- Sharpless and Masamune [1] on one hand, and Nicolaou and Uenishi on the other [2], have developed alternative methods for the enantioselective synthesis of 1,3-diols and, in general, 1, 3, 5...(2n + 1) polyols. One of these methods is based on the Sharpless asymmetric epoxidation of allylic alcohols [3] and regioselective reductive ring opening of epoxides by metal hydrides, such as Red-Al and DIBAL. The second method uses available monosaccharides from the "chiral pool" [4], such as D-glucose. 

Miller also explored the ASD of glycerol derivatives through an enantioselective acylation process which relies on the use of a pentapeptide-catalyst which incorporates an A-terminal nucleophilic 3-(l-imidazolyl)-(5)-alanine residue [171], Most recently, Miller has probed in detail the role of dihedral angle restriction within a peptide-based catalyst for ferf-alcohol KR [172], site selective acylation of erythromycin A [173], and site selective catalysis of phenyl thionoformate transfer in polyols to allow regioselective Barton-McCombie deoxygenation [174],... 

Natural polyols have been used as substrates for the so-called combinatorial biocatalysis , a proposed approach to drug discovery [33]. For instance, complementary enzymatic regioselectivity was applied to produce a combinatorial library of 167 distinct selectively acylated derivatives of the flavonoid bergenin (11) on a robotic workstation [34]. Another lead compound, the antitumoral paclitaxel (12, a molecule with very low water solubility) has been similarly derivatized, initially exploiting the selectivity of the protease thermolysin for its side-chain C-2 OH. 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

Cyclic dibutylstannylene derivatives are convenient intermediates for the regioselective benzylation of polyols.6 These derivatives can easily be prepared by reaction with Bu2SnO or Bu2Sn(OMe)2 with removal of water or methanol, respectively. They can be alkylated in benzene,... 

VIII. Trends in Regioselectivity 1. Symmetrical Diols and Polyols... 

The synthesis of branched saccharides by multiple glycosylations onto a central monosaccharide normally requires the use of orthogonal protecting groups in the acceptor. In this context, regioselective glycosylation of diols or polyols would ease the number of protection-deprotec-tion steps in these synthetic protocols. 

Trialkyltin alkoxides (86) and dialkylstannylene (87) have recently attracted attention because a tin atom attached to an oxygen atom enhances the nucleophilicity of the latter without increasing its basicity. The synthetic applications of tin alkoxides manifest most remarkably in the case of polyols. For example, 1,2,6-hexanetriol was first stannylated with 1 equiv. of (Bu3Sn)20, followed by treatment with benzoyl chloride giving (88) in 67% yield. Intermediacy of the tributyltin ether (89) was proposed for the regioselective benzoylation (Scheme 35). ... 

Selective protection of the primary hydroxy group in polyols by the trityl group can generally be accomplished by the reaction with trityl chloride in pyridine. TTie use of DMAP (0.04 equiv.) and EtsN (1.5 equiv.) facilitates the reaction. " Selective phenylation of one hydroxy group of diols can be carried out by the reaction with triphenylbismuth diacetate. While regioselectivity for primary-secondary vicinal diols is poor, only secondary alcoholic functions are converted to the phenyl ether in secondary-tertiary vicinal diols. Although phenylation of glycols occurs smoothly, monohy oxy alcohols are left essentially intact. ... 

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