Codeinone Dimethyl Ketal and Its Conversion to Thebaine

Rapoport, Henry; Reist, Helen N.; Lovell, Calvin H.

doi:10.1021/ja01600a086

Cited by 8 publications

(3 citation statements)

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“…Rapoport et al [41] [42] reported the synthesis of thebaine from codeinone dimethyl ketal (12). The elimination of methanol from codeinone dimethyl ketal was performed with phosphorous oxychloride in pyridine resulting an 80% yield of thebaine.…”

Section: Synthesis Of Thebainementioning

confidence: 99%

Recent Advances in the Chemistry of Oripavine and Its Derivatives

Hosztafi¹

2014

ABB

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Oripavine is the major alkaloid of Papaver orientale. It is an important intermediate in the biosynthesis of morphine alkaloids. Recently, new Papaver somniferum strains have been developed which accumulate thebaine and oripavine, but not morphine and codeine. Therefore, the chemistry of oripavine has been studied intensively to synthesize opioid pharmaceuticals such as oxymorphone, naloxone and buprenorphine.

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Section: Synthesis Of Thebainementioning

confidence: 99%

Recent Advances in the Chemistry of Oripavine and Its Derivatives

Hosztafi¹

2014

ABB

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“…The first practical synthesis of 1 was reported by Rapoport and his co-workers in 1956 [33], however the procedure was completely described in 1967 (Scheme 2) [34]. Their objective was the preparation of codeinone dimethyl ketal (9) followed by the conversion of the ketal to enol ether.…”

Section: Synthetic Routes To Thebainementioning

confidence: 99%

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

Berényi¹,

Csutorás²,

Sipos

2009

CMC

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The most practical synthetic routes to the preparation of as important pharmaceuticals as oxycodone, naloxone, naltrexone, nalbuphine and buprenorphine have utilized the alkaloid, thebaine, as a starting material. This review intends to focus on chemical transformations of morphinans which resulted in morphinandiene derivatives with well-established and novel pharmacological potencies. These chemical transformations were mainly associated with the formation and substitution of the unique diene structure of the ring C of the morphinan backbone.

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“…There are two problems inherent in the introduction of a 7,8 double bond into 4a. First, the 7 position must be functionalized in the presence of other very reactive positions (C-l, NCH3) and, second, both the 7-functionalized ketone and the ,/3-unsaturated ketone product are labile systems. In the thebaine synthesis7 both of these difficulties were eliminated in a single reaction.…”

Section: Synthesis Of Codeinementioning

confidence: 99%

A practical synthesis of codeine from dihydrothebainone

Weller¹,

Rapoport²

1976

J. Med. Chem.

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The conversion of dihydrothebainone to codeine or thebaine has been achieved in high yield. Bromination and dehydrobromination constructs the 4,5-oxide bridge to give 1-bromo- and 1,7-dibromodihydrocodeinone which yield dihydrocodeinone practically quantitatively after catalytic debromination. Ketalization and acid-catalyzed elimination of methanol give excellent yields of delta6-dihydrothebaine to which is added methyl hypobromite using N-bromoacetamide in methanol. The action of potassium tert-butoxide in Me2SO on the resulting 7-bromodihydrocodeinone dimethyl ketal gives codeinone dimethyl ketal selectivity at 60 degrees while at 120 degrees thebaine is the exclusive product. Hydrolysis to codeinone and borohydride reduction give codeine in 70% overall yield. The bromo intermediates in the formation of the 4,5-oxide bridge have been examined. 1,5beta, 7alpha-Tribromodihydrothebainone has been identified as the main product in the tribromination of dihydrothebainone.

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Codeinone Dimethyl Ketal and Its Conversion to Thebaine

Cited by 8 publications

References 0 publications

Recent Advances in the Chemistry of Oripavine and Its Derivatives

Recent Advances in the Chemistry of Oripavine and Its Derivatives

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

A practical synthesis of codeine from dihydrothebainone

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