1.Structure revision and syntheses of epohelmins A and B.
Snider BB1, Gao X. Org Lett. 2005 Sep 29;7(20):4419-22.
[structures: see text] Epohelmins A (24) and B (26) have been reassigned as pyrrolizidin-1-ols, rather than the proposed 9-oxa-4-azabicyclo[6.1.0]nonane structures 1 and 2, respectively. Syntheses of epohelmin A (24) (eight steps, 52% overall yield) and epohelmin B (26) (11 steps, 43% overall yield) have been achieved starting from N-Cbz-(S)-prolinal (9) and ortho ester ketone 17 using a stereoselective aldol reaction and a stereoselective reductive cyclization as the key steps.
2.Structure-guided minimalist redesign of the L-fuculose-1-phosphate aldolase active site: expedient synthesis of novel polyhydroxylated pyrrolizidines and their inhibitory properties against glycosidases and intestinal disaccharidases.
Garrabou X1, Gómez L, Joglar J, Gil S, Parella T, Bujons J, Clapés P. Chemistry. 2010 Sep 17;16(35):10691-706. doi: 10.1002/chem.201000714.
A minimalist active site redesign of the L-fuculose-1-phosphate aldolase from E. coli FucA was envisaged, to extend its tolerance towards bulky and conformationally restricted N-Cbz-amino aldehyde acceptor substrates (Cbz=benzyloxycarbonyl). Various mutants at the active site of the FucA wild type were obtained and screened with seven sterically demanding N-Cbz-amino aldehydes including N-Cbz-prolinal derivatives. FucA F131A showed an aldol activity of 62 μmol h(-1) mg(-1) with (R)-N-Cbz-prolinal, whereas no detectable activity was observed with the FucA wild type. For the other substrates, the F131A mutant gave aldol activities from 4 to about 25 times higher than those observed with the FucA wild type. With regard to the stereochemistry of the reactions, the (R)-amino aldehydes gave exclusively the anti configured aldol adducts whereas their S counterparts gave variable ratios of anti/syn diastereoisomers. Interestingly, the F131A mutant was highly stereoselective both with (R)- and with (S)-N-Cbz-prolinal, exclusively producing the anti and syn aldol adducts, respectively.
