Enzymatic and chromatographic resolution procedures applied to the synthesis of the phosphoproline enantiomers

Synthesis of Phosphaproline Derivatives: A Short Overview

“…Thus, the reaction of N-protected 2-methoxypyrrolidine with trimethyl phosphite in the presence of boron trifluoride gave the corresponding 2-(dimethoxyphosphoryl)pyr-rolidine as a racemic mixture in 80% yield (Scheme 4, A). 32 Subsequent enzymatic resolution of the racemic mixture allowed the separate (R)-and (S)-enantiomers to be obtained with 82% and 94% ee, respectively. N-Protected 5methoxy-L-proline also reacted with various trialkyl phosphites and triphenyl phosphite to give phosphorylated proline derivatives in up to 61% yield and 85% de (Scheme 4, B); 33 the synthesis of pyrrolidine possessing two phosphoryl moieties in 35% yield and 88% de was also described.…”

Biocatalyzed synthesis of antidiabetic drugs: A review

“…Recently, a kinetic resolution of racaemic Pro P has been described (Arizpe et al 2015), using lipases for the enantioselective synthesis of carbamates, as depicted in Figure 30.…”

“…Nevertheless, separation of these compounds by silicagel column chromatography was not possible, because of the lability of 92, so that the crude obtained from the enzymatic reaction was treated with benzyl 2333 2334 2335 2336 2337 2338 2339 2340 2341 2342 2343 2344 2345 2346 2347 2348 2349 2350 2351 2352 2353 2354 2355 2356 2357 2358 2359 2360 2361 2362 2363 2364 2365 2366 2367 2368 2369 2370 2371 2372 2373 2374 2375 2376 2377 2378 2379 2380 2381 2382 2383 2384 2385 2386 2387 2388 2389 2390 2391 2392 2393 2394 2395 2396 2397 2398 2399 2400 2401 2402 2403 2404 2405 2406 2407 2408 2409 2410 2411 2412 2413 2414 2415 2416 2417 2418 2419 2420 2421 2422 2423 2424 2425 2426 2427 2428 2429 2430 2431 2432 2433 2434 2435 chloroformate to give a mixture of optically active carbamates (S)-94 and (R)-93, which could be separated, and finally (R)-93 was converted into (R)-94. In all cases, the enantiomers could be separated by chiral chromatography (Arizpe et al 2015). These same authors described a somehow simpler protocol by using benzyl 3-methoxyphenyl carbonate for catalyzing the carbamoylation (after 84 h, 82% of (R)-94 and 94% ee of (S)-92), and then an easier separation by a previous tosilation of non-...…”

Lipase-catalyzed dynamic kinetic resolution of dimethyl (1,3-dihydro-2H-isoindol-1-yl)phosphonate

“…1 H, 13 C and DEPT NMR experiments were performed using AV-300 and DPX-300 Brüker spectrometers at room temperature ( 1 H, 300.13 MHz and 13 C, 75.5 MHz). The chemical shifts are given in delta () values and the coupling constants (J) in Hertz (Hz).…”