444313-67-1Relevant articles and documents
cis-4-Alkoxydialkyl- and cis-4-Alkoxydiarylprolinol Organocatalysts: High Throughput Experimentation (HTE)-Based and Design of Experiments (DoE)-Guided Development of a Highly Enantioselective aza-Michael Addition of Cyclic Imides to α,β-Unsaturated Aldehydes
Arenas, Ismael,Ferrali, Alessandro,Rodríguez-Escrich, Carles,Bravo, Fernando,Pericàs, Miquel A.
supporting information, p. 2414 - 2424 (2017/07/22)
A diverse family (37 compounds) of cis-4-alkoxydiorganylprolinol derivatives has been prepared and evaluated in organocatalysis for the first time. The combined use of high throughput experimentation (HTE) techniques with efficient analytical methods has led to the identification of two superior catalysts for the enantioselective addition of succinimide to α,β-unsaturated aldehydes. Further optimization of the reaction conditions with design of experiments (DoE) techniques established the catalyst of choice for the considered aza-Michael reaction, the corresponding adducts (12 examples) being obtained in good yields and excellent enantioselectivities (succinimide and maleimide donors). The synthetic versatility of these Michael adducts is illustrated by a two-step sequence leading to enantiopure 1,3-amino alcohols. (Figure presented.).
Synthesis of a histamine H3 receptor antagonist - Manipulation of hydroxyproline stereochemistry, desymmetrization of homopiperazine, and nonextractive sodium triacetoxyborohydride reaction workup
Pippel, Daniel J.,Young, Lana K.,Letavic, Michael A.,Ly, Kiev S.,Naderi, Bita,Soyode-Johnson, Aki,Stocking, Emily M.,Carruthers, Nicholas I.,Mani, Neelakandha S.
experimental part, p. 4463 - 4471 (2010/10/02)
(Figure presented) We have recently completed the synthesis of 1-[2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(3-fluoro-phenoxy) -pyrrolidin-1-yl]-ethanone, a hydroxyproline-based H3 receptor antagonist, on 100 g scale. The synthesis proceeds through four steps and route selection was driven by a desire to minimize the cost-of-goods. Naturally occurring trans-4-hydroxy-L-proline was chosen as the precursor to the targets core, which necessitated an inversion at both stereogenic centers. The inversions were accomplished through strategic employment of La Rosas lactone and a late-stage Mitsunobu reaction. A first generation synthesis that employed N-Boc-homopiperazine was improved in a second generation approach wherein homopiperazine was directly desymmetrized. Finally, the water solubility of a key intermediate necessitated the development of a nonextractive workup for the sodium triacetoxyborohydride reduction.
Practical syntheses of 4-fluoroprolines
Chorghade, Mukund S.,Mohapatra, Debendra K.,Sahoo, Gokarneswar,Gurjar, Mukund K.,Mandlecha, Manish V.,Bhoite, Nitin,Moghe, Santosh,Raines, Ronald T.
experimental part, p. 781 - 784 (2009/04/04)
4-Fluoroprolines are among the most useful nonnatural amino acids in chemical biology. Here, practical routes are reported for the synthesis of the 2S,4R, 2S,4S, and 2R,4S diastereomers of 4-fluoroproline. Each route starts with (2S,4R)-4-hydroxyproline, which is a prevalent component of collagen and hence readily available, and uses a fluoride salt to install the fluoro group. Hence, the routes provide process-scale access to these useful nonnatural amino acids.
