107599-99-5Relevant academic research and scientific papers
Renin Inhibitors. Design of Angiotensinogen Transition-State Analogues Containing Novel (2R,3R,4R,5S)-5-Amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic Acid
Thaisrivongs, Suvit,Pals, Donald T.,Kroll, Lisa T.,Turner, Steve R.,Han, Fu-Son
, p. 976 - 982 (1987)
A highly stereoselective synthesis of 2(R)--3-methylbutyl>-2,2-dimethyl-4(R)-dioxolanyl>-3-methylbutanoic acid (11) is described.This is a suitably protected carboxylic acid useful as an intermediate for the prepa
Sensing remote chirality: Stereochemical determination of β-, γ-, and δ-chiral carboxylic acids
Tanasova, Marina,Anyika, Mercy,Borhan, Babak
supporting information, p. 4274 - 4278 (2015/04/14)
Determining the absolute stereochemisty of small molecules bearing remote nonfunctionalizable stereocenters is a challenging task. Presented is a solution in which appropriately substituted bis(porphyrin) tweezers are used. Complexation of a suitably derivatized β-, γ-, or δ-chiral carboxylic acid to the tweezer induces a predictable helicity of the bis(porphyrin), which is detected as a bisignate Cotton Effect (ECCD). The sign of the ECCD curve is correlated with the absolute stereochemistry of the substrate based on the derived working mnemonics in a predictable manner.
Conformational preference in bis(porphyrin) tweezer complexes: A versatile chirality sensor for α-chiral carboxylic acids
Tanasova, Marina,Borhan, Babak
supporting information; experimental part, p. 3261 - 3269 (2012/07/01)
Metallated porphyrin tweezers have demonstrated a remarkable ability to function as reporters of absolute stereochemistry for a number of different classes of organic molecules. Flexibility in binding, however, can result in an ensemble of different Exciton Coupled Circular Dichroism (ECCD) active conformations that could lead to variable results. Linker flexibility was found to be a key determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated porphyrin tweezer that yields a common conformational preference for a variety of α-chiral carboxylic acids derivatized with a diamine carrier. Copyright
Monosubstituted γ-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE)
Boy, Kenneth M.,Guernon, Jason M.,Shi, Jianliang,Toyn, Jeremy H.,Meredith, Jere E.,Barten, Donna M.,Burton, Catherine R.,Albright, Charles F.,Marcinkeviciene, Jovita,Good, Andrew C.,Tebben, Andrew J.,Muckelbauer, Jodi K.,Camac, Daniel M.,Lentz, Kimberley A.,Bronson, Joanne J.,Olson, Richard E.,MacOr, John E.,Thompson III, Lorin A.
scheme or table, p. 6916 - 6924 (2011/12/22)
The synthesis, evaluation, and structure-activity relationships of a class of γ-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of γ-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented.
Novel gamma-lactams as beta-secretase inhibitors
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Page/Page column 19, (2010/10/20)
There is provided a series of novel substituted gamma-lactams of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R4, R5 and R6 as defined herein, their ph
Asymmetric synthesis and Lewis acid mediated type II carbonyl ene cyclisations of (R)-2-isopropyl-5-methylhex-5-enal
Braddock, D. Christopher,Brown, John M.
, p. 3591 - 3607 (2007/10/03)
The asymmetric synthesis of (R)-2-isopropyl-5-methylhex-5-enal in 98% ee is described. It was discovered that the key alkylation step employing an Evans chiral auxiliary and 3-methylbut-3-en-1-yl trifluoromethanesulphonate as the alkylating agent led to significant competing O-alkylation, a phenomenon not previously reported. Type II carbonyl ene cyclisation of the aldehyde with a range of Lewis acids led to either the (R,R)- or (R,S)-5-methylidenecyclohexanols without concurrent racemisation of the alpha stereogenic centre of the aldehyde. Conditions for effecting the easy racemisation of a model enantiomerically pure aldehyde, (S)-2-methylbutanal, were developed. In an effort to secure a dynamic kinetic resolution procedure, these conditions were applied to (R)-2-isopropyl-5-methylhex-5-enal. However, a competing and dominant Prins cyclisation occurred instead leading to a mixture of all possible cycloadducts, all of which were obtained in 98% ee. Any unreacted aldehyde was found to be enantiomerically pure. Copyright (C) 2000 Elsevier Science Ltd.
