67315-07-5Relevant academic research and scientific papers
Enantioselective synthesis of (-)-dihydrocodeine and formal synthesis of (-)-thebaine, (-)-codeine, and (-)-morphine from a deprotonated α-aminonitrile
Geffe, Mario,Opatz, Till
supporting information, p. 5282 - 5285 (2015/02/19)
The α-benzylation of a deprotonated bicyclic α-aminonitrile, followed by Noyori's asymmetric transfer hydrogenation combined with the Grewe cyclization onto a symmetrical A-ring precursor, are the key steps of a short and high-yielding enantioselective synthesis of the morphinan (-)-dihydrocodeine. This compound can be converted to (-)-thebaine in high yield by known transformations, while (-)-codeine and (-)-morphine are available from an advanced intermediate. (Chemical Equation Presented).
Chemistry of opium alkaloids, 45. Improvements in the total synthesis of morphine
Meuzelaar, Gerrit J.,Van Vliet, Michiel C. A.,Maat, Leendert,Sheldon, Roger A.
, p. 2315 - 2321 (2007/10/03)
The chiral 1,2,3,4-tetrahydroisoquinoline intermediates in the Price and Beyerman routes to morphine, (+)-(R)-1-(3-hydroxy-4-methoxybenzyl)-6-methoxy- 1,2,3,4-tetrahydroisoquinoline (6) and (+)-(R)-1-(3,5-dibenzyloxy-4- methoxybenzyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline (5), were prepared in high ee by ruthenium-catalyzed asymmetric transfer hydrogenation of the corresponding imine precursors (Noyori method). The yield of the key raw material in the Beyerman route, 3,5-dibenzyloxy-4-methoxyphenylacetric acid (1), starting from gallic acid methyl ester (7) was improved by a factor of 5 over previously described syntheses. Key steps in the new procedure are the selective formation of methyl 3,5-dihydroxy-4-methoxybenzoate (9) via the 3,5-diacetate and an improved benzylation of the hydroxyl groups in 9.
General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes
Kitamura,Hsiao,Ohta,Tsukamoto,Ohta,Takaya,Noyori
, p. 297 - 310 (2007/10/02)
In the presence of a small amount of RuX2[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4- tetrahydroisoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100%) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation conditions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used for synthesis of salsolidine. This enantioselective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction.
Synthesis of racemic and chiral codeine and morphine via the dihydrothebainones. (Chemistry of opium alkaloids, part XI)
Lie,Maat,Beyerman
, p. 419 - 420 (2007/10/11)
Racemic and chiral 1-(3,5-dibenzyloxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-6-methoxy-isoquinoline (1, Scheme) were N-methylated, which gave 2a. A Birch reduction converted 2a, via 2b, into the 1,4-diene 3. Acid-catalysed cyclization of 3 gave the morphinan 4. Selective removal of the hydroxyl group in position 2, via the 1-phenyl-5-tetrazolyl ether (5), by hydrogenolysis, yielded (-)-dihydrothebainone-(6). The conversion of 6 into (-)-codeine and (-)-morphine is known. In this way our preceding synthesis is shortened by two steps.
