Alkaloids photochemical deriv

The photochemical reaction of tertiary amines with C6o can be used to synthesize alkaloid-C6o derivatives [269], Irradiation of alkaloids bearing a tertiary amino group such as tazettine, gramine, scandine, or 10-hydroxyscandine with C6o led to the isolation of alkaloid-C6o adducts. Use of tazettine and gramine in the reaction yielded the expected [6,6] adduct. In addition to the pyrrolidinofullerene 94a-b, a new type of monoadduct 95a-b with a bis-[6,6] closed structure characterized by UV-vis, FT-IR, II-NMR, 13C-NMR, II- II-COSY, ROESY, HMQC, and HMBC spectroscopy was obtained from the reaction with scandine 93a and its 10-hydroxy derivative 93b (Scheme 38). 

Dihydrothiazoloquinoline is a key intermediate in the synthesis of natural sulfur-containing pyridoacridine alkaloids—kuanoniamines and derdercitins, where the starting dienone is converted after a multistep reaction sequence to an a-bromo-ketone, which in turn was cyclized with thiourea to the desired dihydrothiazoloquinoline, photochemically convertible to the final alkaloid derivatives 39 (Scheme 21) (92JA10081, 95TL4709, 95JA12460). 

Other examples of photochemical transformations of nitrones into alkaloids have been described (461). According to the view of the authors, some trans-oxaziridines give products derived from the trapping of aminyl radicals (AR) by the pendant alkenes (Scheme 2.90). 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The protoberberine alkaloid, xylopinine, has been synthesized in an optically active form by Kametani et al.22 ). A key reaction in this synthesis was the photochemical cyclization of the optically active amino acid derivative 1,2,3,4-tetrahydro-6,7-dimethoxy-3-methoxycarbonyl-1 -methylene-2-veratroylisoquinoline with 1,3... 

The photochemical electrocyclic reaction of acrylamides represents a versatile strategy for alkaloid synthesis. Thus, (S)-pipecoline has been synthesized using the photochemical cyclization of enantiomerically pure acrylamide derivatives in the presence of NaBH4, which causes reduction of the imonium intermediate. The lactam may then easily be transformed into the desired heterocyclic compound (Scheme 9.26) [38]. 

Likewise, benzyldihydroisoquinolinium derivatives can be used in a photochemical synthesis of tetrahydroisoquinolines. Thus, 2-(2-trimethyl-silylmethylphenylmethyl)-3,4-dihydroisoquinoliniun perchlorates have been successfully cyclized, as in the synthesis of the protoberbine alkaloids (+)xylopinine and (+)stylopine. The reaction proceeds via SET from the xylyl donor to the iminium moiety, fragmentation of the benzylsilane radical cation and carbon-carbon bond formation in the intermediate diradical. The synthesis is rather general and the yields compare favorably with those obtained from related substrates via a dipolar cycloaddition methodology [298] (Sch. 27). 

A photochemical preparation of a Cephalotaxus alkaloid synthon (20) has been reported (Scheme 2).10 The readily accessible maleimide (17) was iodinated with iodine and silver trifluoroacetate, in 71% yield, and the resulting compound was transformed in two steps (70% overall yield) into the methylene-pyrrolone (18) by the action of methylmagnesium iodide followed by dehydration. Irradiation of (18) afforded (19) (46% yield), which, by successive hydrogenation and reduction with lithium aluminium hydride, gave the dihydro-pyrrolo[2,l-b][3]benzazepine (20). This derivative has served as a key intermediate in the total synthesis of cephalo-taxine described previously (see Vol. 7 of these Reports). 

This chapter reviews the synthesis of alkaloids and related compounds by the use of photochemical or thermal cyclization reactions of conjugated systems, unconjugated systems structurally related to or derived from what... 

The aziridine derivative 117, a photochemical valence tautomerization product of berberinephenolbetaine, was also converted into the benzindan-oazepines by regioselective C-14—N bond cleavage (Scheme 24)." The treatment of 117 with p-toluenesulfonic acid in benzene under reflux gave rise to the benzindenoazepine 118 whose N-methylation with dimethyl sulfate in HMPA in the presence of sodium hydride afforded the n-methyl derivative 119." Since 119 has already been converted" to ( )-c -alpini-genine (120) and ( )-ds-alpinine (121), this synthesis constitutes a formal synthesis of these alkaloids. 

A photochemical ring construction similar to that described in Scheme 5 was used in the synthesis of the aromatic lycorine alkaloid ungeremine (51) (Scheme 6). Photocyclization of the somewhat inaccessible imine (48) gave the phenanthridine derivative (49) in 21 % yield which upon metal hydride reduction and cyclization with phosphorus tribromide afforded the quaternary salt (50) which was shown to be identical with the methyl ether of ungeremine (51) obtained as shown. 

Several of the condensations with aromatic aldehydes have been used in the synthesis of alkaloid systems. 2-Nitrobenzaldehydes have been used in synthetic routes to 7-hydroxyaporphines/°° and 2-iodobenzaldehydes have been used in oxidative photochemical routes to the aporphines and oxoapor-phines caaverine, isoboldine, corunnine, and nandazurine. ° The aldehyde 46 has been used with the anion of the Reissert compound derived from... 

A further use of Barton esters has been described as a path to enol ether radicals. The reaction involves the photochemical decomposition at 355 nm of the derivative (85). As part of an approach to the synthesis of a series of Kopsia alkaloids, the reductive decarboxylation of the derivative (86) was carried out. This involved irradiation of the Barton ester (86a) in the presence of t-BuSH. This affords the product (86b). The photochemical decomposition of the Barton ester (87) provides a path to the silyl derivatives (88). The nature of the trapping agent X is dependent on the conditions under which the reaction is carried out. Thus a variety of derivatives can be obtained using alcohols to afford ethers, or using ethanesulfonyl azide to give azides. The Barton esters (89) undergo the usual photochemical decarboxylation to afford ethenoyloxy radicals. Cyclization within these, in the presence of tributylstannane yields the lactones (90). ... 

The photochemical behavior of the W-oxides of the Cinchona alkaloids has been examined 49). Photolysis (> 300 nm) of the aromatic mono-iV-oxides 183 of the dihydro derivatives of quinine, quinidine, cincho-nidine, and cinchonine in alcoholic solvents gave the expected carbo-styrils 186 in yields of 70-85%. The same results were obtained with the corresponding AjiV-dioxides 184. An interesting rearrangement was observed in the case of the iV,A -dioxides of dihydrocinchonine and dihydrocinchonidine. Photolysis in benzene solution afforded, in addition to the carbostyrils, the iV -formylindole methanols 188 in 30% yield. The hydrolysis-sensitive benz[d]-l,3-oxazepines 185 were proposed as the probable intermediates. 

The degradation of 2,2-dimethylisoquinolinium iodides 101 was carried out for the synthesis of phenanthrene alkaloids. Hoffmann elimination of the quaternary ammonium salt gave a stilbene intermediate 102 (Scheme 45), which was used as substrate for a photochemical electrocyclization to afford phenanthrene derivatives 103 in moderate to good yields <04TL4171>. 

Nitrogen-containing heterocyclic enone systems also reacted with allene to give (2 + 2)-cycloadducts, as was shown in alkaloid synthesis.178 As the keystep in the synthesis of an annotinine derivative, allene was added to 157 and the adduct 158 was obtained in quantitative yield. Various uracils have been modified by photochemical (2 + 2)-cycloaddition with olefins, e.g., vinylene carbonate,17,18° vinyl ethers, vinyl acetates, and (cetene acetals yielded 159.181 Very recently the photochemical addition of cyanoethylenes to 2-pyridones has been observed to yield mixtures of tetrahydroazocin-2-ones (160) and (2 + 2)-cycloadducts (161).182... 

Dihydrooxepino[3,2-a]carbazole derivatives are formed in moderate to rather high yields on photochemical rearrangement of pyranocarbazole alkaloids, for example mahanimbine <88TL6625>. 

An intramolecular SrnI reaction was used as key step in the synthesis of the alkaloid 0-demethyleupoularamine 3. The intermediately formed SrnI product is readily transformed by photochemical oxidative biaryl formation and subsequent methylation to the target compound 3 in good yield (Equation 13.7) [23]. The SrnI cyclization of l-(2-bromobenzyl)-l,2,3,4-tetrahydroisoquinolin-7-ol derivatives 4 was recently applied to the synthesis of aporphine alkaloids 5 (Equation 13.8) [24] and, by using the same approach, homoaporphine alkaloids can also be synthesized. 

The l-fiT-pyrano[3,4-c]pyridine nucleus is found extensively amongst alkaloids and a short photochemical synthesis has been reported, starting from readily available 4-acetoxy- or 4-alkoxy-2-pyridones (54). Under photochemical stimulation, these compounds react with the diethyl acetal of acrolein. Treatment of the head-to-tail adducts (55) with a base gives the cyclobuta[c]pyridone derivative (56), which rearranges (upon heating in acid) to produce the H-pyrano[3,4-c]pyridone (57). The method is claimed to be general. 

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