L-Selectride as a General Reagent for the O-Demethylation and N-Decarbomethoxylation of Opium Alkaloids and Derivatives¹

Abstract

L-Selectride was shown to be an efficient and general O-demethylating agent for the opium alkaloids and their derivatives and also an efficient reagent for the cleavage of methyl carbamates, thus offering a convenient method for the N-demethylation of opioids. Further, it was shown that by choice of reaction conditions it is possible to achieve both N-decarbomethoxylation and O-demethylation in one pot, or only render N-decarbomethoxylation in high yield without accompanying O-demethylation.

Recent Developments in the Chemistry of Thebaine and its Transformation Products as Pharmacological Targets

“…In Fig. (11) three important transformations of oripavine (22) are presented resulting in 14 -hydroxymorphinone (24) [75], an effective and frequently used opiate receptor agonist, orvinone (25) …”

First Synthesis and Utilization of Oripavidine – A Concise and Efficient Route to Important Morphinans and Apomorphines

“…-In this work, we present a novel strategy for the synthesis of several important dopamine D 2 agonists and the successful extension of the method for the preparation of 14b-hydroxy-6-ketomorphinan derivatives. Coop and Rice developed the first one-pot O-and N-deprotection procedure applying the previously formed N-(carbomethoxy)normorphinans [4]. The only restriction of this method is that in morphinans having a C(8)¼C (14) bond the formation of corresponding N-methoxycarbonyl derivative is always accompanied with the cleavage of the C(9)ÀN(17) bond [5].…”

“…Despite several references to the preparation of compound 7, its detailed characterization has not been presented. The title compound was prepared from thebaine (6, 1000 mg, 3.21 mmol) according to the procedure described in [4] with 9 h of refluxing and 2 h of cooling periods ( Table 1 (1)); 115.07 (C(2)); 110.62 (C (8)); 96.73 (C (7)); 90.42 (C (5) (6)); 55.46 (MeOÀC(3)); 54.04 (C (9)); 49.93 (C(16)); 43.99 (C (13) 7,8,8 · HCl). The title compound was prepared from compound 7 (1000 mg, 2.06 mmol) in line with the previously described procedure [4], however, the reflux period was 9 h, and the cooling period was 2 h ( Table 1).…”

“…We found that, with the application of the method described by Coop and Rice, compound 8 was isolated in 44% yield as a HCl salt [4]. However, the optimization of Scheme 1.…”

Lithium tri-sec-Butylborohydride (l-Selectride): A Powerful and Highly Stereoselective Reducing Reagent

“…16 It was also found to be an efficient reagent for the desymmetrization of mesodiesters, 17 dehalogenation of monohalopyridines, 18 rearrangement of 5-trimethylsilylthebaine, 19 reductive cleavage of exoxides, 20 and deprotection of N-carbomethoxysubstituted opioids to N-noropioids. 21 Lithium tri-sec-butylborohydride is commercially available, but can also be readily prepared by addition of tri- 23 Various enantiomerically pure aziridino ketones can be stereoselectively reduced by L-Selectride to provide the corresponding alcohols with high diastereoselectivities and yields. 24 L-Selectride is also employed for the reduction of steroidal aldehydes.…”