Bacillus subtilis epoxide hydrolase-catalyzed preparation of enantiopure 2-methylpropane-1,2,3-triol monobenzyl ether and its application to expeditious synthesis of (R)-bicalutamide

Chemoenzymatic Approach to Enantiomerically Pure (R)‐3‐Hydroxy‐3‐methyl‐4‐pentenoic Acid Ester and Its Application to a Formal Total Synthesis of Taurospongin A

“…CuI (0.171 g, 0.898 mmol) was added under the flow of N 2 . The reaction temperature was raised to À50 8C, 3 [3] (0.811 g, 4.55 mmol) in dry THF (0.4 mL) was added to the reaction mixture and stirred for 3 h. After the mixture had been warmed to room temperature, a saturated aqueous solution of NH 4 Cl (10 mL) was added to the dark-colored mixture reaction. The mixture was diluted with EtOAc, and then the combined organic layer was washed with brine, dried over Na 2 SO 4 and concentrated in vacuo.…”

“…[3] This was treated with vinylmagnesium chloride in THF in the presence of CuI to give (R)-4a in almost a quantitative yield. Next, the benzyl protective group in 4a was selectively removed, by treatment with lithiumethylenediamine-THF, [4] a modified Benkeser reduction.…”

“…While amidases had in many cases worked enantioselectively on b-alkoxy-and acyloxy-substituted nitriles, [16][17][18][19] the loss of stereoselection had also been observed when the substituent was altered from alkoxy and/or acyloxy to a hydroxy group. [16,[20][21] In this case, as the antipodal substrate, (S)-5 can be prepared from the enantiomerically pure form of (R)-epoxide 3, [3] this total procedure in Scheme 2 and Scheme 3 would also work well to provide (S)-1b.…”

“…While so far (R)-2a in an enantiomerically pure state has been available [1] by means of microbial epoxide hydrolase-catalyzed enantioselective hydrolysis of readily available racemic epoxide 3, [2] we also reported the use of an over-expressed Bacillus subtilis epoxide hydrolase (Scheme 1). [3] All the transformation steps should be carried out under the mildest conditions possible without any loss of the enantiomeric excess of the product. Otherwise, as the target molecule 1 has rather labile tertiary alcoholic hydroxy group at the b-position, it would be susceptible for elimination-addition of water or retro-aldol and aldol condensation of the molecule.…”

Epoxide Hydrolases and their Application in Organic Synthesis

“…Enantiopure epoxides and diols are chiral intermediates or building blocks, which can be used for the synthesis of biologically active compounds such as antibi otics [4], antifungal drugs [5], antiandrogens [6], receptor agonists and antagonists [7][8][9], 11-heterosteroids [10], HIV protease inhibitors [11,12], nonsteroidal antiinflammatory drugs [13,14], and other natural products [15][16][17][18][19]. An EH-triggered cascade reaction enabled the asymmetric synthesis of two antitumor agents, which occur naturally in Panax ginseng [20].…”