Navigation

0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest. Please login or sign up for a free trial to access the full content.
40.1.1.5.1.2.1 Variation 1: Enzymatic Kinetic Resolution

DOI: 10.1055/sos-SD-040-00265

Azov, V. A.Science of Synthesis, (200940421.

In contrast to selective enzymatic acylation and deacylation of alcohols, which has become an effective and widespread technique for the preparation of optically enriched compounds in laboratory practice and in industry, the corresponding enzymatic kinetic resolution of amines is less developed. This disparity originates from two fundamental differences between alcohol and amine resolution: (1) due to the higher nucleophilicity of amines, blank nonenzymatic acylation should be taken into account; (2) hydrolysis of the acylated product is much more difficult in the case of amides compared to esters. Nevertheless, significant progress has been made in the enantioselective enzymatic acylation of amines since the early 1990s (for a review on kinetic enzymatic resolution of amines see ref[‌11‌]) and this has paved the way for a practical application of the method, even on a multiton industrial scale with production capacity of up to 2500 tons per year achieved by BASF in the resolution of rac-1-methoxypropan-2-amine.[‌10‌]

Mee eeeeeeeeee eeeeee eeeeeeee eee eeeee, eeeeeeeeeee ee eee eeeeeee eeeee ee Meeeee 8 eeeeeeee eeeeeeee ee M8 eeee M8: eeeeeeeeeeeeeeee eeeeeeeee eeeeeeeee ee eeeeeee 88 eeeeeeee ee eeeeeeeeee ee (M)-88 eee eeeeeeeeee ee eee eeeeeeee eeeeeee (M)-88 ee eeee eee eeeeee eeeee eeeeeeeeee (M)-88. Mee eeeeeee eeeeeeeeee eeeeee, eeeeeeeeeeeeeeee eeeeee-eeeeeeee eeeeeeeeee ee eee eeeeeee eeeeee eeeeeeee eeee eeeeeee eeeeee, ee eeee eeee eeeeee. Me eeeeeeee e eee-eeee eeeeeeee eeeeeeee eee eeee eeeeeeeeeeeeee ee eee eeeeee eeeeeeee eee eeeeeee eeeeee eee eeee eeeeeeeeee eeeeee.

Meeeee 8 Meeeee-Meeeeeee Meeeeee Meeeeeeeee ee Meeeee Meeeee

Mee eeeeeeeeee eeeeeeeeeee ee eee eeeeee eee eeeeeeeee eeeeeeeeeeee eeee ee ee eeeeeeeee.[‌88‌,‌88‌] Meeee, eee eeeeeeeee eeeeeee eeeeee eee eeeee eeeeeeeeeeeee eeee eeeeee ee ee eeeee eee eeeeeeeeee eeeeee ee eeeeeeeeeeee eeeee eeeeeee eeeeeeeeee (eeee eeeeeeee eee/ee eee ee e eeeeeeee-eeeeeeeeeee eeeeeee); eeeeeeeee, ee eeeeeeeeeee eeeeeeeeee eeeeeeee eeee eeeeeeee eee eeeeeeeeeeee eeeeee ee eee eeeeeee. Meeeee, eee eeeeeeee eeeeeee eeeeee eeeeeeeee e eeeeeee eeeeeeeee eeeee eeeeeeeeee eeeee[‌88‌] eeeeeeee eeeeeeeeeeeeeee eeeeeeeeeeee ee eee eeeeeee eeeeeeeeee ee eeee eeeeeeeeee ee eeeeee. Meeeeeeee, eeeeeeee eeee eeee eeeeeee eeeeeeeee eeeeeeeeee eeeeee eeee ee eeee-8-eeeeeee (eeee 88[‌88‌]), eeeeeeeeeeeeeeeee (eeee 88[‌88‌,‌88‌,‌88‌]), ee eeeeeeeeeeeeeeee (eeee 88[‌88‌,‌88‌] eee 88[‌88‌]) eee eeeeeeeee. M eeeee ee eeeeeeeee eeeeeeee 8888 ee eeeeeeeeeee ee Meeeee 8.

Meeeee 8 Meeeeeeee Meeeeeee Meee ee Meeeeeeee Meeeeee Meeeeeeeee[‌88‌‌88‌,‌88‌‌88‌]

Meeeeee, eee eeeee-eeeeeeeeeee eeeeeee eeeeeeeee, eee eee eeee eeeeeeee eeee eeeeeee eee eeeeeeeeeeeeeeee eeeeeeeee ee eeeeee.[‌88‌,‌88‌,‌88‌‌88‌] Meeeeee eee eeeeeeeeee eeeeee eeeeeee eee eeeeeeee eeeeeeeee eeeeeee eeeeeeee eeeeee eeee. Mee eeeeeeeee eee ee eeeeeee ee eeeeeee­eee eeeee eeeeeeee eeeeeeeeeeeeee ee e eeeeeee eeeeeeee, eeee ee eeeeeee eeeee ee eeeeeeeeeee eeeeeeeeeeeee. Meee eeeeeeeee eeeeeee eeeeeee Meeeeee eeeeeeeeee eeeeee M (MMMM), eeeee ee eeeeeeeeeeee eeeeeeeee ee eeee eee eeeeeeeeeee eeeee eeee eeeeeee eeeeeeeee. Mee eeeeeee, eeeeeee 8-eeeeeeee-8-eeeeeeee 88 eee eeeeeeeeeee eeeeeeee eeee eeee eeeeee, eeeeee eee M-eeeeeeeeee eeeeee eee eee eeeeeeeeeeeee M-eeeeeeeeee eeeeeeeeee 88 (Meeeee 8). Mee eeeee eeeeeee ee eee eeee eeeeee eeeeeeeee eeeeee, eeeeeeeeee[‌88‌] eee eeeeeeeeee eeeeeee,[‌88‌] eeee eeeeeeee eeee eeee eeeeeeeee, eeeeeeee eeee eeee eeee eeeeeeeee eeeeeeeee eee eeeeeeeeeeeeeeee eeeee eeeeeeeee.

Meeeee 8 Meeeeeeeee ee eee-8-Meeeeeee-8-eeeeeeee Meeee Meeeeee eeeeeeeeee Meeeee M[‌88‌]

Meeeeeeeeee 8

M8 Meee (e) ee (%) ee (M)-88 Meeeee (%) ee (M)-88 ee (%) ee (M)-88 Meeeee (%) ee (M)-88 ee (%) ee (M)-88 Meeeee (%) ee (M)-88 Mee
M 88 88 88 >88 88 88 88 [‌88‌]
8-Me 88 88 88 >88 88 88 88 [‌88‌]
8-M 88 88 88 88 88 88 88 [‌88‌]
8-M 88 88 88 >88 88 88 88 [‌88‌]
8-Me 88 88 88 88 88 88 88 [‌88‌]
8-Me 888 88 88 [‌88‌]

e Meeee eee eeeeeeeee eeee ee eeeee ee e 88% eeeeee ee eee eeeeeee eeeee eee eeeeee ee eeeeeeee eee eeeeeeee eeeeeeeee.

e Meeee ee eee eee eeeeeeeeee eeee ee eeeeeeeee (M)-88 eee eeeeee ee eeeeeeee eee eeeeeeee eeeeeeeee.

Meeeeee eeeeeeee,[‌88‌] eeee ee eeeeeee, eeeeee, eeeeeeeeeeeeeee, eeeeeee, eee eeeeeee eee eeeeeeeeeee eeeee eeee eeee eeee eee eeeeeeeee eeeeeeeee. Meeeeeeeee eeeeeeeeeee eeeeeeeeee ee eeee eeeeee[‌88‌] ee eeeeee eee eeeeeeeeeeeee eeee eeee eeee eeee eeeeeeee. Meeee eeeeee ee eeeee ee e eeeeeeee eeeeeee eee eeee ee eeeeeeeeeee eeeeeeeeee ee eee eeee eeeee (ee eeeeeeee ee eee eeeeeeeee eeeee eeee, eee eeeeeeeee eeee eee eeeeeeee eeeeeeee ee eee eeeeee), eeeeeeeeee ee eeeeeeeeee eeeeeee eee ee eeeeeeeee eeeee. Meee eeeeeeeeee eeeeeeee eeee eeeee e eeeeeeeeee eee eee eeeeeeeee eeeeeeeeeeeeeeee eeeeeeeeee ee eeeeee eeeeee ee eeeeeee eeeee.[‌88‌,‌88‌]

M eeeeeee ee eeeeee eeeeee,[‌88‌,‌88‌,‌88‌‌88‌] e.e. 88 (Meeeee 8; eee Meeeeee 88.8.8.8.8.8), ee eeee ee 8888 (Meeeee 8), eeee eeee eeeeeeeee ee eeeee ee eeeeeeeee eeeeeee eeeeeeeeee; eee eeeeee eeeeee e eeee eeeeeee eeeee ee eeeeeeeeee ee ee eeee eeeeeeee eeee eeeeeeeeeeeeee eeeeeeeeeeeeeee. Meeeee ee >8888% (eeeee ee e 88% eeeeee ee eeeeeeee eeeeeee eeeee) eee eeeeeee eeeeeeee eee eeee eeeee eee eeeeeeeee eeeee eeeeeeeeee; eeee eeee eeeeee ee eeeeeeeeeeee eeeeee (8888%) eee eeeee eeeeeeee. Mee eeeeeeeeee ee eeeeeeeee eeeee eeee eeeeeeeeee eee eee eeeeee eeeeeeeee e eeeeeee ee eeeeee eeeeeeeeeeee eeee ee eeeeee eee eeeeee eeeee, eeeeeeeee, eeeeeeeeeeeeeee, eeeeeeee, eee eeeeee. Meeeeeeeee ee α- eee β-eeeee eeeeee eee eeee eeee eeeeeeee,[‌88‌] eeeeeeee eee eeeeeeee eeeeee ee eeeeeeeee eeee eeeeeee eeeee eee eeeeee eee eeeee eeeeeeeeee ee eee eeeee eeeeeeeeeeeee.

Meeeee 8 Meeeeeeeeeeeee Meeeeeeeee ee Meeeee Meeeee Meeeeeeee ee Meeeeeeee Meeeeee Meeeeeeeee[‌88‌‌88‌,‌88‌‌88‌]

Mee eeeee eeeeeeee ee eee eeeeeeeee eeeeeeeee eeeeee ee eeee eeeeeeeeee ee eeeeeeeee eeeeee ee eeeee eeeeeeeeeee (eeee e eee eeeeeeee eee eeeeeeee[‌88‌]) eee eeeeeeeeee ee eeeeeeee eeeeee ee eeeeeeeeee. Mee eeeeeeeeee ee eeeeeeeee eeeeee e eeeee-eeee eeeeeeeee eeeeeeeee eeeeeeeeeeeeeeee eeeeeeeee eeeeeeeeee ee eeeeeeee eeeee eeeeee ee eeeeeeeee eee eeeeeeeee eee eeeeeeeeeeee eeeeeeee ee eeeeeee eeeeeeeee eeeeee eeee eeee eeeeeeeeeeee eeeeee eee eeeeee eee eeee eeeeeeeeeee.[‌88‌] Mee eeeeeee, eeeeeee 8-eeeeeeeeeeeeeee (88) ee eeeee eeeeeeee eeee eeeee eeeeeeeeeeeeeeee ee eeeeeee 88 (Meeeee 8). Mee eeeeeeeee ee eeeeeeee eeeeee eeeeeeee ee eeeeeee eeee eeee eeeeee eee eeeeeeee eeeeee, eee ee eeeeeeeeeeeeeee eeeeeeeeeeee ee eeeeeeee. Meeeeeeeee eeeeeeeee eeeeeeeeee eeeee eeeeeeeee eeeeeeeeeeeeeeeeee eee eeee eee eeee (M)-88 eee eeeee (M)-88, eeeeeeeee eeeeeeeee eeee eeeeee (M)-88 eee (M)-88 eeeee eeeeeeeeeeee ee (M)-88 eee (M)-88 ee eeeeeeeee eeee 8M ­eeeeeeeeeeee eeee.

Meeeee 8 Meeeeeeeeeeeee Meeeeeeeeee ee Meeeeeeeeeeeeeee Meee (M)- eee (M)-8-Meeeeeeeeeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

(M)- eee (M)-8-Meeeeeee-8-eeeeeeee 88; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee eeeeeee 8-eeeeeeee-8-eeeeeee eee-88 (8eeee), MeMMe (8.88eM, 8eeee), eee eeeeeeeeeee Meeeeee eeeeeeeeee eeeeee M (Meeeeee 888) (888ee) ee Me8M (8eM) eee eeeeeee ee ee eeeee eee eeeeeeee eee eeeeeeeee ee MM ee e MM-eeeeeeee MMMM M/M eeeeee. Meeee eee eeeeeee eeeeeeeeee (ee. 88%) eee eeeeeeee, eee eeeeeee eee eeeeeee eeee Me8M eee eeeeeeee ee eeeeee eee eeeeee. Mee eeeeeee eeeee eee eeeeee eeee 8.8M MMe (8 ×), eee eee eee eeeeee eeee eeeeeeeee. Mee eeeeeee eeeee eeeeeeeeee eee eeeee eee eeeeee eeee eeee eeeee, eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee ee eeee eeeee (M)-88. Mee eeeeeee eeeee eeeeeeeeee (M)-88MMe eee eeee eeeeeeee ee eM 88 eeee eeeee MeMMM8 eee eeee eeeeeeeee eeee Me8M (8 ×). Mee eeeeeee eeeee eee eeeeee eeee eeeee, eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee ee eeee eeeee (M)-88. Mee eeeee eeeeeeee eeee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 8:8). Mee eeeeeeeeeeeee ee eee eeeeeeee eeeeeeee eee eeeeeeeeee ee MM ee eee eeeee-eeeeeeeee eeeeee eeeeee.

M eeeeeeeeee ee M-(8-eeeeeeee-8-eeee)eeeeeeeee (M)-88 (8eeee) eee 8.8M ee MMe (8.8eM) eee eeeeee ee 88°M eee eee eeeeeeee eeee (888e). Mee eeeeeeeee eeee eee eeeeeeeee eeee Me8M (8eM). Mee eeeeeee eeeee eee eeee eeeeeeee ee eM 8.8 ee eeeeeeee ee eeeee MeMMM8 eee eeeeeeeee eeee Me8M (88eM). Mee eeeeeeee eeeeeee eeee eee eeeee (M8MM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeee/Me8M 8:8 eeee Me8M), eeeeeeeee eeee (M)-88.

References