Synthesis chirality

Chirahty at the phosphoms is an unavoidable problem in all phosphorothioate syntheses. The phosphoramidite method produces a mixture of both the and the diastereomers having a small excess of the isomer (53). Although some progress has been made in the chiral synthesis of dinucleoside phosphorothioates, low yields have limited the utility of these approaches. The chiral center may be eliminated by replacing the other, nonbridging oxygen with sulfur. Avoidance of the chirahty problem is one reason for the interest in phosphorodithioates. 

A second, conceptually distinct chiral synthesis of monobactams was developed from P-hydroxy amino acids. As shown in Figure 2, cycli2ation of the acylsulfamate of an amino-protected 0-mesylserine derivative (14, R = H) leads directiy to the monobactam (15). This methodology was also appHed to the synthesis of 4a- (15, R = CH ) and 4P-methyl monobactams from L-threonine and aHothreonine, respectively (17). The... 

A final example of this synthetic methodology is the chiral synthesis of the cyclopenta[c]pyridine ring system of (-)-plectrodorine 43. Oxazole 41 was heated in o-... 

Consonant with the present interest in chiral synthesis, two additional contributions can be cited. Sih al utilized a combined microbiological and organic chemical sequence in which key chirality establishing steps include the conversion of to chiral, but unstable, 18 by enzymic reduction using the fungus Diplodascus uninucleatus. Lower side-chain synthon was prepared by reduction of achiral with Pencillium decumbens. 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, fS -( - -3-methyl-3-( 3 -nitrovinyl -o-valerolactone Scheme 8 11 shows a total synthesis of f-i-physosdgmine, a principM alkriloid of the CMabar bean The key nitroalkene is prepared by asymmetric nitroolefinadon of ct-methyl-o-lactone using a chirM enamine fsee... 

Further utility of the Andersen sulphoxides synthesis is demonstrated by the preparation of optically active unsaturated sulphoxides which were first prepared by Stirling and coworkers359 from sulphinate 276 and the appropriate vinylic Grignard reagents. Later on, Posner and Tang360 prepared in a similar way a series of ( )-l-alkenyl p-tolyl sulphoxides. Posner s group accomplished also the synthesis of (+)-(S)-2-(p-tolylsulphinyl)-2-cyclopentenone 287, which is a key compound in the chiral synthesis of various natural products361 (equation 159). 

Keywords bis(oxazoiine) copper complexes, Lewis-acid catalysts for carbo-cyclic and hefero-Diels-Alder reaction, chiral synthesis... 

This suite of BVMOs is available via whole-cell expression systems and represents a complementary platform of biocatalysts for diverse applications in chiral synthesis. Representatives of this collection were utilized in the enantiodivergent synthesis of the indole alkaloids alloyohimbane and antirhine from a fused bicyclic precursor (Scheme 9.19) [151]. 

The regiochemical course reacting saturated ketones depended on the substitution pattern of the a-positions. In most cases, the intermediate oxime had an anti N-OH function with respect to the chain branched a-position. Consequently, the more substituted alkyl group preferentially migrates. This advantage was utilized for synthesizing the spiro a-amino-e-caprolactam (202 203, Scheme 38) [12c], the Mexican bean beetle azamacrolide allomone (205 206, Scheme 39) [44 a], in a key step of the chiral synthesis of benzomorphanes... 

Up to the present, fifteen enantiomers have been synthesized among the thirty-two carba-sugars theoretically predicted. Four of them have been prepared from the antipodes of the Diels-Alder adduct 29, two were obtained from quebrachitol, and a chiral synthesis, starting from true sugars, provided the thirteen enantiomers. 

Among the known enantiomers of carba-sugars, thirteen have been synthesized by a chiral synthesis starting from a true sugar the four modifica-... 

The above sequence was demonstrated on racemic onti-mercaptol alcohol 14 as well on a small amount of optically pure 14 (separated by chiral HPLC separation) and the chiral centers of 14 were completely retained, as expected (Scheme 5.6) [8]. With proof of concept for the ring formation strategy, some efforts were put into developing a chiral synthesis of 14, as shown in Scheme 5.7. 

The Cp2TiPh-catalyzed coupling reaction of the dials also gives the cyclic diols with excellent diastereoselectivity. The protocol is extended to the chiral synthesis as shown in Scheme 16 [50,51]. 

Chiral Synthesis of Pharmaceutical Intermediates Using Oxynitrilases... 

Hydroxynitrile lyases (HNLs or oxynitrilases) catalyze C—C bond-forming reactions between an aldehyde or ketone and cyanide to form enantiopure cyanohydrins (Figure 1.15), which are versatile building blocks for the chiral synthesis of amino acids, hydroxy ketones, hydroxy acids, amines and so on [68], Screening of natural sources has led to the discovery of both... 

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. 

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