Reduction with sodium borohydride without protecting groups

Reductions with Sodium Borohydride Without Protecting Groups 

A solution of 7.2 g of sodium borohydride (analyzing at 87 % purity) in 300 ml of pyridine is added dropwise, with vigorous stirring, over 7 hr to a solution of 50 g of pregnane-3,11,20-trione in 100 ml of pyridine and 18 ml of water. The temperature is kept at 18-20°. The stirring at this temperature is continued for another 2 hr, after which the reaction mixture is poured slowly into dilute hydrochloric acid (575 ml of cone hydrochloric acid in 5.2 liters of water) and the stirring continued for 1 hr. The precipitate is filtered, washed with 

The benzene mother liquors are evaporated in vacuo to dryness, and the residue is recrystallized from butyl acetate to give 33.3 g of 3a-hydroxypreg-nane-11,20-dione, mp 173-173.5° [aj 113° (1% solution in CHCI3). Taking into account the recovered triketone, the total yield is 70.4%. 

21-Trihydroxypregn-4-ene-3,11-dione 21 -acetate from Cortisone Acetate  

Paper chromatography (benzene-chloroform 1 1—formamide system) of representative chromatogram fractions indicates the presence of a small quantity of a more polar ultraviolet absorbing component that gives a negative blue tetrazolium test and a very polar component (no ultraviolet negative tetrazolium test). These materials have not been characterized. 

---

A. Reductions with Sodium Borohydride Without Protecting Groups... 

Reduction with sodium borohydride without protecting groups, 92 Reductive deacetoxylation of ll-keto-12/3-hydroxytigogenin diacetate, 53 Reductive methylation of the 3-ethylene ketal of pregna-5, 16-diene-3, 20-dione, 54... 

Chiral intermediates for the synthesis of (-)-anisomycin (1) and (+)-anisomycin (anti-1) (153), (R)-2-(p-methoxyphenyl)methyl-2,5-dihydro-pyrrole (142) and its (S)-isomer (+)-187, have been efficiently synthesized from D-tyrosine and L-tyrosine, respectively (Scheme 20) [28]. D-tyrosine was converted to 0-methyl D-tyrosine methyl ester (182) [72-75] which was treated with di-tert-butyl dicarbonate to protect the amino group. Subsequent reduction of the ester group with sodium borohydride in the presence of lithium chloride furnished the alcohol 183. Swern oxidation of 183 followed by chain extension with the anion derived from bis(2,2,2-trifluoroethyl)(ethoxycarbonylmethyl)-phosphonate afforded (Z)-Q ,/0-unsaturated ester (184), which was used immediately without purification to avoid or minimize any possible racemization of the chiral center. Reduction of the ester group of 184 with diisobutylaluminium hydride afforded the alcohol 185 which after mesylation followed by intramolecular cyclization gave the desired 2,5-dihydropyrrole derivative 186. Removal of the tert-butyloxycarbonyl group was achieved by treatment with trifuoroacetic acid to give (-)-142 in 62% overall yield from 182. The (S)-2,5-dihydropyrrole (-l-)-187 was also prepared in the same manner starting from L-tyrosine. Since (-l-)-187 had been transformed into (-l-)-anisomycin (anti-1) (153), (-)-142 could also be transformed to the (-)-anisomycin (1) [26,66]. 

Conversion of alditols to aldoses without the need to protect all hydroxy groups has been achieved by monotosylation of one primary hydroxy group, displacement with azide ion and photolysis in methanol to yield the aldimine,which was then hydrolyzed to the aldose. The procedure was illustrated using 3 4-0 isopro ylideno-D-mannitol to produce D-mannose. The synthesis of D-[U- Cjgalactose from methyl <-D-[n- Cjglucopyranoside via aqueous bromine oxidation to the 4.-uloside, reduction by sodium borohydride and hydrolysis has been described, along with the isolation of D-glucuronic acid and methyl o( D-mannopyranoside as by-products. 

---