148433-01-6Relevant articles and documents
Formal total synthesis of aliskiren
Peters, Byron K.,Liu, Jianguo,Margarita, Cristiana,Andersson, Pher G.
, p. 7292 - 7296 (2015)
The efficient and selective formal total synthesis of aliskiren is described. Aliskiren, a renin inhibitor drug, has received considerable attention, primarily because it is the first of the renin inhibitor drugs to be approved by the FDA. Herein, the formal synthesis of aliskiren by iridium-catalyzed asymmetric hydrogenation of two allylic alcohol fragments is reported. Screening a number of N,P-ligated iridium catalysts yielded two catalysts that gave the highest enantioselectivity in the hydrogenation, which gave the saturated alcohols in 97 and 93 % ee. In only four steps after hydrogenation, the fragments were combined by using the Julia-Kocienski reaction to produce late-stage intermediate in an overall yield of 18 %.
Synthesis of new α-aminophosphonate derivatives incorporating benzimidazole, theophylline and adenine nucleobases using l-cysteine functionalized magnetic nanoparticles (LCMNP) as magnetic reusable catalyst: Evaluation of their anticancer properties
Bahrami, Foroogh,Panahi, Farhad,Daneshgar, Fatemeh,Yousefi, Reza,Shahsavani, Mohammad Bagher,Khalafi-Nezhad, Ali
, p. 5915 - 5924 (2016/02/05)
A new class of structurally diverse α-aminophosphonate derivatives containing benzimidazole, theophylline and adenine heterocycles were synthesized using a simple and efficient strategy. This class of α-aminophosphonates was synthesized using the reaction
Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers
Kamal, Ahmed,Prabhakar,Janaki Ramaiah,Venkat Reddy,Ratna Reddy, Ch.,Mallareddy,Shankaraiah, Nagula,Lakshmi Narayan Reddy,Pushpavalli,Pal-Bhadra, Manika
experimental part, p. 3820 - 3831 (2011/11/12)
Aiming to develop multitarget drugs for the anticancer treatment, a new class of chalcone-pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) conjugates linked through a 1,2,3-triazole moiety containing alkane spacers has been designed and synthesized. Combining the
The nonchiral bislactim diethoxy ether as a highly stereo-inducing synthon for sterically hindered, γ-branched α-amino acids: A practical, large-scale route to an intermediate of the novel renin inhibitor aliskiren
Goeschke, Richard,Stutz, Stefan,Heinzelmann, Walter,Maibaum, Juergen
, p. 2848 - 2870 (2007/10/03)
The diastereoselective synthesis of the sterically hindered, γ-branched α-amino acid derivative (2S,4S)-24a and its N-[(tert-butoxy)carbonyl](Boc)-protected alcohol (2S,4S)-19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)-17 was obtained by alkylation of the chiral Schoellkopf dihydropyrazine (R)-12a with the dialkoxy-substituted alkyl bromide (R)-11a, which proceeded with explicitly high diastereofacial selectivity (ds > 98%) to give (2S,SR,2′S)-13a (Scheme 4), followed by mild acid hydrolysis and N-Boc protection (Scheme 5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)-11a with the enantiomeric (S)-12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeO-C(6) and the bulky residues of (R)-11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)-11a was found to provide a 95:5 mixture of diastereoisomers (2S,2′S)-22a and (2R,2′S)-23a in high yield (Scheme 6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)-24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)-28a and (R)-28b with both (R)-12a and (S)-12b as well as with the achiral 21 was investigated (Schemes 7-9). The precursor bromides (R)-11a, (S)-11b, (R)-28a, and (S)-28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)-7a and (S)-7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes 3 and 7). A practical and economical protocol of the preparation of (2S,4S)-24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N-protected γ-branched α-amino acid with (2S) absolute configuration.
Radical isomerization via intramolecular ipso substitution of aryl ethers: Aryl translocation from oxygen to carbon
Lee, Eun,Lee, Chulbom,Tae, Jin Sung,Whang, Ho Sung,Li, Kap Sok
, p. 2343 - 2346 (2007/10/02)
Bromopropyl aryl ethers an converted to 3-arylpropanols under standard radical generating conditions in the presence of tributylstannane and AIBN. This rearrangement involves intramolecular ipso attack of the alkyl radicals which generates spiro cyclohexadienyl radical intermediates.
