Methyl olivetolate

Further syntheses of [4",5"- H2]- and [4",5"- H2]-A -THC and -A -THC have been described (c/. Vol. 7, p. 50), and Crombie et al. have extended miniaturized synthesis and chromatographic analysis (c/. Vol. 6, p. 49) to cannabinoid esters,large-scale syntheses of which using acid-catalysed terpenylation of methyl olivetolate have also been described ester cleavage, using lithium n-... 

Resorcinols. Condensation of this diene with the ketal of a fi- keto acid derivative results in a resorcinol with complete regiocontrol. Thus, the TiCl4-catalyzed reaction of 1 with ketal ester 2 results in the resorcinol 3 in 72% yield. However, use of the acid chloride 4 corresponding to 2 in the same reaction results in the isomeric resorcinol, methyl olivetolate (5). The regiocontrol is based on the reactiv ity order acid chloride > ketal > ester. The resorcinol 5 was used in a biomimetic synthesis of the chromene A1 -tetrahydrocannabinol (6), a component of marijuana. 

A synthesis of (—)-A -tetrahydrocannabinol has been achieved using the cycloaromatization reaction of the l,3-bis(trimethylsilyloxy(butadiene (130) with the S-dicarbonyl equivalent 140 to generate methyl olivetolate 141 with complete... 

Methyl olivetolate (140) and its regioisomer (141) have been prepared in a regiocontrolled manner by the condensation of (63) with the two 1,3-electrophiles (142) and (143) respectively (Scheme 48). - - In these cases, the reactivity order in the electrophilic components is acid chloride > acetal > ester. This reaction has been used in a biomimetic synthesis of (-)-A -tetrahydrocannabinol (144). 

NaHC03 and recrystallize from acetonitrile. Dissolve 4.3 g (T) in 30 ml anisole and add 0.1 M methyl Mgl in 50 ml anisole. Stir 12 hours and evaporate in vacuum or acidify with sulfuric acid, neutralize with NaHC03 and filter wash to get 2.4 g N-benzyl analog of THC. For other N-analogs of unknown activity see JOC 3(5,2995(1968). Recover unreacted olivetol as usual. 

A closely related methodology (route c) involves the dianion from a diketone (R = Me) with the anion of dimethyl malonate (R = Me) (ref.25). The bis-trimethylsilyl ether from methyl acetoacetate has been interacted with the ketalised acid chloride shown (R = CgH ) to furnish the methoxy carbonyl derivative of olivetol (route d) (ref.26). It was also found that pentane-2,4-dione with dimethyl malonate in the presence of sodium hydride afforded methyl orsellinate (ref.26). In a biomimetic approach (route e) a tetraketone has been enzymically cyclised to give the corresponding orsellinic acid (R=H, R = alkyl) (ref. 27). 

Olivetol-dy. The synthetic procedure of Pitt l. (6) was used with some modifications to increase the incorporation of deuterium. Methyl 5-(3,5-dimethoxyphenyl)penta-2,4-dienoate was reacted with LiAlDi+ followed by hydrogenation with D using the catalyst tris(triphenylphosphine)rhodium chloride. The 5-(3,5--dimethoxyphenyl)pentan-l-ol-l,1,2,3,4,5was then reacted with PBr3, LiAlDii, and BBr3 according to Pitt. (6) to yield... 

Olivetol-dp, A -THC-dp, CBD-d, and CBN-dp. The methyl ester of 3,5-dimethoxybenzoic acid was reduced with LiAlD and the obtained alcohol was reacted with PBr3. The bromide was mixed with Cu(l)I and butyllithixmi to yield 0,0-dimethylolivetol-l , 1 ia, showed the deuterium content (m/e 180 - 182) 0.3%,... 

By condensation of 2,4-dibenzyloxy-6-methylbenzoic acid and benzyl 4-benzyloxy-3-(2, 4 -dihydroxy-6 -methyl-benzoyloxy)-6-hydroxy-2-methylbenzoate with TFAA and subsequent debenzylation From 4-benzyloxy-2-hydroxy-6-/i-pentylbenzoic acid and olivetol with DCCD and subsequent debenzylation From 2-hydroxy-4-methoxy-6-n-propyl-benzoic acid and divarol with DCCD From 2-hydroxy-4-methoxy-6-n-propyl-henzoic acid and 3-methoxy-5-n-propylphenol with DCCD From 4-benzyloxy-2-hydroxy-6-n-pentyl-benzoic acid and 3-methoxy-5-n-propylphenol with DCCD and subsequent debenzylation... 

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