D-pantoyl lactone

The hydrogenation of ketones with O or N functions in the a- or / -position is accomplished by several rhodium compounds [46 a, b, e, g, i, j, m, 56], Many of these examples have been applied in the synthesis of biologically active chiral products [59]. One of the first examples was the asymmetric synthesis of pantothenic acid, a member of the B complex vitamins and an important constituent of coenzyme A. Ojima et al. first described this synthesis in 1978, the most significant step being the enantioselective reduction of a cyclic a-keto ester, dihydro-4,4-dimethyl-2,3-furandione, to D-(-)-pantoyl lactone. A rhodium complex derived from [RhCl(COD)]2 and the chiral pyrrolidino diphosphine, (2S,4S)-N-tert-butoxy-carbonyl-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine ((S, S) -... 

ASYMCTRIC HYDROGENATION OF KETOPANTOYL LACTONE D-(-)-PANTOYL LACTONE... 

The submitter claims that tetrahydrofuran can also be used giving D-(-)-pantoyl lactone with 83.3-84,8% ee. This was not checked. 

D-(-)-Pantoyl lactone 1s a key intermediate for the synthesis of pantothenic acid which is a member of the vitamin B-complex and is an important constituent of Coenzyme A. Although D-(-)-pantoyl lactone has been obtained by classical optical resolution using quinine, ephedrine, and other chiral amines, catalytic asymmetric synthesis appears to be more effective... 

D-(-)-pantoyl lactone with 95-100% ee. However, the isolation procedure from aqueous media in these microbial reductions, i.e., extraction, recovery of raw materials, and purification, is very troublesome because of the high solubility of the product in water. Consequently, the present method has considerable advantages from a synthetic point of view, e.g., (i) the yield of the reaction is virtually 100%, and (n) isolation of the product is simple and convenient since the reaction is carried out in small amounts of nonaqueous media. 

Ketopantoyl lactone 2,3-Furandione, dihydro-4,4-dimethyl (8,9) (13031-04-4) D-(-)-Pantoyl lactone 2(3H)-Furanone, dihydro-3-hydroxy-4,4-dimethyl -,... 

I. Ojima, T. Kogure, and Y. Yoda 18 ASYMMETRIC HYDROGENATION OF KETOPANTOYL LACTONE D-(-)-PANTOYL LACTONE... 

Asymmetric reduction of prochiral carbonyl compounds for the production of chiral alcohols D-pantoyl lactone production by... 

ASYMMETRIC REDUCTION OF PROCHIRAL CARBONYL COMPOUNDS FOR THE PRODUCTION OF CHIRAL ALCOHOLS D-PANTOYL LACTONE PRODUCTION BY ASYMMETRIC REDUCTION... 

The development of a novel production system for D-pantoyl lactone (which is a lactone compound carrying a chiral hydroxy group and a chiral intermediate for the commercial production of D-pantothenate) by microbial asymmetric reduction has been undertaken. D-pantothenate is mainly used in various pharmaceutical products and as an animal feed additive, the current world production of calcium pantothenate being about 6,000 tons per year. Conventional commercial production of D-pantoyl lactone has depended exclusively on chemical synthesis involving optical resolution of a chemically synthesized racemic pantoyl lactone, which is the most troublesome step of the pantothenate synthesis process. 

D-pantoyl lactone (Fig. 19.2). This type of hydrolysis reaction is catalyzed by many filamentous fungi such as Fusarium oxysporum. Since the reaction seemed to be a promising one for the enzymatic resolution of racemic pantoyl lactone, the enzyme responsible for this hydrolysis was characterized in some detail. 

Hata, H., Shimizu, S., and Yamada, H. 1987. Enzymatic production of D-(-)-pantoyl lactone from ketopantoyl lactone. Agric. Biol. Chem., 51, 3011-3016. 

D-Pantoyl lactone Carbonyl reductase (Candida parapsilosis) 350 (100)... 

This asymmetric induction was used to obtain d-( — )-pantoyl lactone (7), the microbiological precursor to D-(-)-pantothenic acid (8). The key step, reduction... 

We found in our laboratory, a novel lactonohydrolase that catalyzes reversible hydrolysis of various lactones including aldonate lactones and aromatic lactones. The enzyme was crystallized from Fusarium oxysporum and characterized. It has been shown that the enzyme hydrolyzes only D-pantoyl lactone, a chiral intermediate for the commercial production of D-pantothenate, in a racemic mixture of pantoyl lactone and that the enzyme is very useful for the optical resolution of racemic pantoyl lactone (Fig. 3)7. When F. oxysporum mycelia entrapped in calcium alginate gel were incubated in 30% solution of DL-pantoyl lactone, almost stoichiometric hydrolysis of D-pantoyl lactone was observed. After repeated reactions for 150 times over 150 days, the mycelia retained more than 90% of their initial activity. A 1,000... 

Figure 3. Comparison of enzymatic and conventional resolution processes for DL-pantoyl lactone. DL-PL, DL-pantoyl lactone D-PL, D-(-)-pantoyl lactone L-PL, L-(+)-pantoyl lactone D-PA, D-(-)-pantoic acid L-PA, L-(+)-pantoic acid.

This recrystallization is very temperature sensitive, e.g., this purification was done at ambient temperature (28-30°C). The first recrystallization removes 3.7 g of d,T-pantoyl lactone and 0.2 g of D-(-)-pantoyl lactone. When the recrystallization was done at 5°C, twice as much solvent served to remove only 4.2 g of d,i-pantoyl lactone and none of the D-isomer. 

Ketopantoyl lactone 2,3-Furandione, d1hydro-4,4-dlmethyl (8,9) (13031-04-4) D-(-)-Pantoyl lactone 2(3H)-Furanone, dihydro-3-hydroxy-4,4-d1methy1 0- (8) 2(3H)-Furanone, d1hydro-3-hydroxy-4,4-dimethyl- (9) (599-04-2) Ch1oro(l,5-cyclooctadiene)rhodium (I) dimer Rhodium, di-v-ch1orobis(l,5-cyclooctadiene) di- (8) Rhodium, di-y-chiorobis[(1,2,5,6- )-l,5-cyclooctadiene] di- (9) (12092-47-6)... 

They found that the enantioselectivity of the reaction is highly influenced by the steric bulkiness of the substituents in the phosphine, while electronic factors play only a minor role. Working with the Rh-BPPM catalytic system R = tBuO), 86.7% optical yield was achieved under optimum reaction conditions, enabling the preparation of pure D(—)-pantoyl lactone in a single recrystallization step. 

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