Spiro compounds, alkaloids, synthesis

Diarylamides with arenes activated by electron-donating substituents can be converted to azacycles by anodic oxidation through phenolic oxidative coupling reactions that can be a key step in the synthesis of alkaloids (Schemes 16 and 17). According to the nature of substituents and the experimental conditions, either spiro compounds [22] or non-spiro compounds [23, 24] were obtained. 

An oxidative spiroannulation reaction was carried out for simple phenols and as a result good yields of spiro-compounds containing tetrahydrofuran rings were obtained <02TL3597>. In the stereospecific and enantiospecific total synthesis of the sarpagine indole alkaloid dehydro-16-epinormacusine B, an oxidative cyclization of the alcohol shown below was the key and final step <02OL4681>. 

A homoveratryl enaminone derived from cyclohexane-1,2-dione was cyclized through a 1,4-addition at the a,/ -unsaturated ketone moiety of the enaminone319 (equation 237). The spiro compound obtained, which is a useful intermediate in the synthesis of erythrina-alkaloids, demonstrates the special character of a-ketoenamines. 

Alkaloids having a spiro-fused ring system, such as sesbanine and gramme, were also the targets of synthesis by the use of enamide photocycli-zation. Gramain et al. (49,50) succeeded in synthesizing various types of the spiro compounds 261 and 262 by applying nonoxidative photocycli-zation of the enamide 260 prepared from cyclohexanecarboxaldehyde (Scheme 93). 

Kita et al. found that phenolic oxidative coupling in case of 272 provides seven-membered N heterocyclic compounds 274 and 275 by bond shift of the initially formed spiro intermediate 273 under suitable conditions. Besides 274 and 275, piperidino-spiroquinone 276 is also formed in this oxidation (Scheme 68). Of particular interest is the recently developed synthesis of amaryllidaceae alkaloids such as (+)-maritidine (Scheme 69) (96JOC5857). 

The synthesis of quinolizidine (3-spiro-2 )-tetrahydrothiophene (67a, 67b), a model compound for the synthesis of dimeric sulfur alkaloids, was reported (65, 66). The compound was prepared from 2-cyanotetrahydrothiophene (66) by two independent routes, both utilizing phase-transfer catalysis (Scheme 10). 

In the Erythrina series, Tsuda and co-workers11 have developed new methods for the synthesis of spiro-type compounds that are related to Erythrina alkaloids, either by intramolecular nucleophilic cyclization of dioxopyrrolines or by cycloaddition of activated butadienes to dioxopyrrolines. The conversion of 2-(ethoxycarbonyl)-cycloalkanones (9) into the spiro-type compounds (12), in high yield, via 3,3-disubstituted dioxopyrrolines (11) is shown in Scheme l.12 They also reported... 

Related work not directly dealing with total synthesis of proaporphine, aporphine, or homoproaporphine alkaloids has appeared. A series of homopro-aporphine-type compounds (110) have been prepared, as shown in Scheme 9.12 7 Compound (106), readily prepared from 3,4-dimethoxy-/ -phenethylamine and the appropriate keto-acid derivative, was transformed by reduction and acetylation to (107). Acetylation effectively blocked any complications from the cyclohexane oxygen function during the subsequent Bischler-Napieralski cyclization. Consecutive reduction, alkylation, and hydrolysis gave the key intermediate (109) which was transformed into the tetracyclic spiro-system (110) by reaction with polyphosphate ester under strictly defined conditions. Other conditions and... 

The heterocyclic spiro-oxindole moiety is found in a large number of alkaloids, which are important pharmaceutical compounds [44]. Several synthetic protocols are reported in the literature for the synthesis of these compounds [45]. Recently, Tao et al. [46] developed a direct asymmetric domino Michael/reduction/cychzation sequence for the construction of spiro[2H-pyran-3,4 -indohne] 99 from isatyhdene malononitrile 97 and acetone 98 in the presence of the chiral compound 100 (Scheme 9.20). 

Spirooxindole derivatives are of considerable interest because of their broad biological properties. They are also structural motifs found in many classes of alkaloids and medicinal privileged compounds. In 2011, Macaev and coworkers demonstrated that (-)-(5)-brevicoUine (a p-carboline alkaloid) can be used, in a cycloaddition process, to catalyze one-pot multicomponent synthesis of spiro[oxoindole-3,4 -4 ... 

Ma and coworkers reported a similar reaction for the synthesis of spiro-3,4-dihydropyranes [44]. The reaction between cyclic p-oxo aldehydes and aromatic p,Y-unsaturated a-ketoesters catalyzed by the cinchona alkaloid derivatives afforded the corresponding spirocyclic compounds in good yields and moderate to good enantioselectivities. 

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