- Alkene chemoselectivity in ring-closing metathesis: A formal synthesis of (-)-periplanone-B
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A synthesis of the (-)-dienone 1 (R = Pr(i)) via ring-closing alkene metathesis to give the substituted dihydropyran 13 in the presence of alkenyl iodide functionality is described.
- Hodgson, David M.,Foley, Anne M.,Lovell, Peter J.
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- A Stille cyclisation approach to (-)-periplanone-B: Studies in alkene-selective ring-closing metathesis and an improved chromium(II)-mediated synthesis of (E)-alkenylstannanes from aldehydes
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A synthesis of the dienone 7 via an efficient intramolecular Stille cross-coupling reaction, an improved chromium(II)-mediated synthesis of (E)-alkenylstannanes from aldehydes using Bu3SnCHI2 in DMF, and a synthesis of the substituted (-)-dienone 25 via ring-closing alkene metathesis to give dihydropyran 22 are described. The synthesis of (-)-dienone 25 constitutes a formal synthesis of (-)-periplanone-B. The Royal Society of Chemistry 1999.
- Hodgson, David M.,Foley, Anne M.,Boulton, Lee T.,Lovell, Peter J.,Maw, Graham N.
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- The development of a complementary pathway for the synthesis of aliskiren
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The synthesis of aliskiren (1), a recently marketed drug for the treatment of hypertension, is presented. The focus of our synthetic effort is to develop an efficient pathway for the synthesis of (2S,7R,E)-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy) benzyl)-N,N,8-trimethylnon-4-enamide (2a), which has been used as the advanced intermediate toward aliskiren. After an extensive investigation of three different strategies designed to construct the E-olefin functionality in 2a by employing the olefin cross-metathesis, Horner-Wadsworth-Emmons (HWE), and Julia-type olefinations, we have established a new protocol for the synthesis of 2a with a substantially improved overall efficiency in terms of the yield (ca. 33%), and diastereo- and E/Z-selectivity. The key transformations were the Evans chiral auxiliary-aided asymmetric allylation for the synthesis of the appropriate chiral intermediates in excellent enantiomeric purity of higher than 97% ee and a modified Julia-Kocienski olefination for the highly selective construction of E-2a with up to 13.6:1 E/Z ratio from the chiral intermediates. Consequently, the results provide an appealing option for the synthesis of aliskiren. This journal is
- Li, Le-Le,Ding, Jin-Ying,Gao, Lian-Xun,Han, Fu-She
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supporting information
p. 1133 - 1140
(2015/03/03)
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- A total synthesis of aliskiren
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A total synthesis of aliskiren (20) was accomplished. A key in our synthesis was to use the symmetric trans-cisoid-trans-bis-lactone 1 as a precursor. It was expediently prepared by three different routes (Scheme 2). Appending the end groups and functional group transformations completed the synthesis (Scheme 3). Copyright
- Nam, Gyeok,Ko, Soo Y.
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p. 1937 - 1945,9
(2012/12/12)
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- A new synthesis of the orally active renin inhibitor aliskiren
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A convergent synthesis of the orally active renin inhibitor aliskiren (1) is described. The synthesis was accomplished in 12 steps starting from the known chloride 2. The key step involves the Curtius rearrangement of the advanced intermediate 15, which provides lactone/carbamate 17 containing the correct stereochemistry and all of the functionality required for the preparation of the drug substance.
- Slade, Joel,Liu, Hui,Prashad, Mahavir,Prasad, Kapa
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scheme or table
p. 4349 - 4352
(2011/08/22)
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- Total synthesis of 10-isocyano-4-cadinene and its stereoisomers and evaluations of antifouling activities
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The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, and determination of its absolute stereochemistry were achieved. 10-Isocyano-4-cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, intermolecular Diels-Alder reaction and samarium diiodide induced Barbier-type cyclization were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined as (1S,6S,7R,10S) by comparison of the optical rotations between natural and synthetic samples. In addition, the authors successfully synthesized 10-epi- and di-1,6-epi-10-isocyano-4-cadinene through the same synthetic pathway. Antifouling activities against Balanus amphitrite with the cadinenes were also evaluated.
- Nishikawa, Keisuke,Nakahara, Hiroshi,Shirokura, Yousuke,Nogata, Yasuyuki,Yoshimura, Erina,Umezawa, Taiki,Okino, Tatsufumi,Matsuda, Fuyuhiko
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body text
p. 6558 - 6573
(2011/10/05)
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- Process and intermediates for the preparation of aliskiren
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The present invention relates to a process and intermediates for the manufacture of aliskiren or pharmaceutically acceptable salts thereof.
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Page/Page column 23
(2010/06/15)
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- Total synthesis of "Aliskiren": The first renin inhibitor in clinical practice for hypertension
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We report a "macrocycle route" toward aliskiren, a drug presently marketed for the treatment of hypertension, using a highly stereocontrolled approach starting from a common "isopropyl chiron". Highlights of the synthesis include a challenging RCM reaction to produce a nine-membered unsaturated lactone, a highly stereoselective catalytic Du Bois aziridination, and a regio- and diastereoselective aziridine ring-opening to a vicinal amino alcohol.
- Hanessian, Stephen,Guesne, Sebastien,Chenard, Etienne
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supporting information; scheme or table
p. 1816 - 1819
(2010/09/16)
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- ORGANIC COMPOUNDS
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The present invention relates to olefin metathesis processes for the manufacture of a compound of the formula (I) which is a novel useful intermediate in the synthesis of pharmaceutically active compounds, in particular renin inhibitors.
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Page/Page column 52
(2009/01/23)
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- A convenient synthesis of chiral β3-amino acids
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A novel method for the synthesis of chiral β3-amino acids is developed where the acid functionality was built by oxidative cleavage of an α-allylic group that was introduced by Evans' asymmetric alkylation of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.
- Chakraborty, Tushar K.,Ghosh, Animesh
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p. 2039 - 2040
(2007/10/03)
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- A convergent synthesis approach towards CGP60536B, a non-peptide orally potent renin inhibitor, via an enantiomerically pure ketolactone intermediate
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We report a convergent synthesis of the potent orally active non-peptide renin inhibitor CGP60536B. The key reaction employs the coupling of the enantiopure Grignard species derived from chloride 13 with the diastereomerically pure γlactone 9b. The stereoselective reduction of the resulting ketone 14b has been thoroughly investigated. (C) 2000 Elsevier Science Ltd.
- Rueger,Stutz,Goschke,Spindler,Maibaum
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p. 10085 - 10089
(2007/10/03)
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