DMAP

DMAP

Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum.[Pubmed:27155463]

Eur J Med Chem. 2016 Aug 25;119:34-44.

A DMAP catalyzed synthesis of new 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines was studied, in a view to react 4-chloroquinazolines with poorly nucleophilic alcohols such as benzylic alcohols, via a simple and cheap SNAr reaction approach. A fast (1 h) general operating procedure, affording good reaction yields, was achieved under microwave irradiation. Thus, a series of 35 molecules was obtained and evaluated in vitro on the K1 multi-resistant Plasmodium falciparum strain, in parallel with a cytotoxicity assessment on the human HepG2 cell line. 5 hit-molecules were identified, presenting both promising antiplasmodial activity (1.5 muM < IC50 < 2 muM) and low cytotoxicities (25 muM < CC50 < 45 muM). Apart for 2 molecules, the global series displayed a satisfying solubility in the aqueous biological media. Structure-activity relationships showed that the molecules presenting a benzyloxy moiety were less cytotoxic than the ones bearing a phenoxy moiety at position 4 of the quinazoline ring. It also appeared that the introduction of a heteroaryl moiety afforded inactive compounds. Finally, the most active and selective molecules (Selectivity Index = 22-27) were the ones presenting either an unsubstituted benzyloxy group or a phenoxy group, this last bearing a p-bromo or an o-acetyl substituent.

First DMAP-mediated direct conversion of Morita-Baylis-Hillman alcohols into gamma-ketoallylphosphonates: Synthesis of gamma-aminoallylphosphonates.[Pubmed:28144364]

Beilstein J Org Chem. 2016 Dec 30;12:2906-2915.

An efficient synthesis of a series of gamma-ketoallylphosphonates through a direct conversion of both primary and secondary Morita-Baylis-Hillman (MBH) alcohols by trialkyl phosphites with or without DMAP, used as additive, and under solvent-free conditions, is described herein for the first time. Subsequently, a highly regioselective Luche reduction of the primary phosphonate 2a (R = H) gave the corresponding gamma-hydroxyallylphosphonate 5 that further reacted with tosylamines in the presence of diiodine (15 mol %) as a catalyst, affording the corresponding SN2-type products 6a-d in 63 to 70% isolated yields. Alternatively, the alcohol 5 produced the corresponding acetate 7 which, mediated by Ce(III), was successfully converted into the corresponding gamma-aminoallylphosphonates 8a-d.

Beyond a Protecting Reagent: DMAP-Catalyzed Cyclization of Boc-Anhydride with 2-Alkenylanilines.[Pubmed:27163704]

J Org Chem. 2016 Jun 3;81(11):4645-53.

A novel rapid synthesis of quinolines from 2-alkenylanilines has been described; the reaction involves an unexpected DMAP-catalyzed cyclization of 2-alkenylanilines with di-tert-butyl dicarbonate (Boc2O, 2.0 equiv), and a series of tert-butyl quinolin-2-yl carbonate with various functional groups have been synthesized in good yields under mild conditions. Furthermore, the tert-butyl quinolin-2-yl carbonate can be easily converted into corresponding quinolinones and 2-(pseudo)haloquinolines.

Development of a Chiral DMAP Catalyst for the Dynamic Kinetic Resolution of Azole Hemiaminals.[Pubmed:28060519]

J Org Chem. 2017 Jan 20;82(2):869-886.

A new catalyst for the dynamic kinetic resolution of azole hemiaminals has been developed using late-stage structural modifications of the tert-leucinol-derived chiral subunit of DMAP species.