Prenyl amine

Prenyl amine (66) was long used in the treatment of angina pectoris, in which condition it was believed to act by inhibiting the uptake and storage of catecholamines in heart tissue. Droprenilamine (69), an analogue in which the phenyl ring is reduced, acts as a coronary vasodilator. One of several syntheses involves simple reductive alkylation of 1,1-diphenyl-propylamine (67) with cyclohexyl acetone (68)... 

In contrast to nitroglycerin and pentaerythritol tetranitrate, coronary vasodilators such as dipyridamole s and chromonar increased total coronary blood flow in dogs without redistributing blood flow or improving endocardial oxygen tension. The coronary vasodilators, dipyridamole, chromonar, lidoflazine, iproveratril, papaverine and prenyl amine were all shown to exert a selective dilator action on small coronary arteries and arterioles. 

Icmt catalyzes the methyl esterification of the prenylated cysteine residue after Reel has proteolyzed the -CaaX-containing proteins. The first step in identification of the minimal substrate for Icmt was through identification of AFC (Figure 9.2) as described above. Interestingly, farnesylcys-teine (FC), which is devoid of the acetyl substitution, was not a substrate but did possess some activity as an inhibitor [51], suggesting that the free amine of FC requires modification for catalytic turnover. Alterations in the stereochemistry about the FC backbone also appeared to be detrimental to substrate activity. The stereoisomer, d-AFC, was not a substrate for Icmt but was a modest mixed-type inhibitor of the enzyme. AFC-methyl ester (AFC-Me) was also reported to be a mixed-type inhibitor with respect to both l-AFC and -adenosylmethionine (SAM), the methyl donor, with Ki values of 41 and 73 pM, respectively [52,53] The farnesyl homocysteine homolog of AFC is not a substrate for the enzyme however, the racemic DL-homocysteine farnesyl derivative is in fact a weak inhibitor [40]. Similar to the results with racemic prenylcysteine, these data demonstrate that the linker between the carboxylate and thioether moieties is critical for substrate activity. 

DeaUylation. The nickel-catalyzed reaction is applicable to a wide range of amines, 5-membered A-heteroaromatic compounds, amides, and sulfonamides. Ally ether cleavage is also facile and selective (with TBS, Bn, MOM, THP, Ac, Bz, Piv, An, and prenyl derivatives of alcohols intact). ... 

An enantioselective synthesis of amino acids has been examined using chiral nonracemic a-imino esters (36) derived from (S)-l-phenylethylamine and (-)-l-cyclohexylethylamine (equation 9, Table 9). Allyl-magnesium, -copper and -titanium reagents react at both the imine and ester carbon atoms of (36), a result of the molecule s ambient electrophilicity. The addition of allyl-, methallyl- and prenyl-9-BBN and -ZnBr to a-imino ester (36), however, generates amines (38) and (39). While the absolute stereochemistry of (38) and (39 R = Ph) has been determined (entries 1-4, Table 9), that of the cyclohexyl-ethylamine-derived products has not (entries 5-8, Table 9). 

The synthesis starts from the A-Boc-tyrosine methyl ester, which was O-benzylated, since the prenyl ether required in the target compound is not compatible with the conditions required for the preparation of the hydoxylamine or the hydrogenation of the isoxazolidine intermediate (Scheme 40). Following cleavage of the A-Boc, the resulting primary amine was treated with anisaldehyde, and after oxidation with m-CPBA... 

The synthesis of 4 involves ten initial steps to achieve alcohol 54 from tyrosine (16% overall yield) and pursues with the change of the alkyl side chain on the phenolic hydroxyl group (Scheme 46). Thus, O-demethylation of 54 followed by prenylation and treatment of the resulting lactam with LiAlH4 gaves azaspiranic compound 149. Protection of the secondary amine and oxidation of both alcohols using TPAP/NMO lead to the keto aldehyde 150. Treatment of the latter with Cd/Pb couple [78] allows the deprotection of the secondary amine as well as the cyclization process to provide (+)-TAN1251C (4). 

Furoquinoline alkaloids specifically labeled with 14C in the furan ring were required for biosynthetic studies (see Section VII of this chapter), and since existing routes produced low yields, Grundon and co-workers (195, 196) developed a more efficient synthesis from 4-methoxy-3-prenyl-2-quinolones 244-246. These compounds had previously been prepared from aromatic amines and substituted malonates, but direct allylation is more suitable for the preparation of labeled compounds, employing, for example, [14C]-3,3-dimethylallyl bromide. It was found that reaction of... 

The traditional procedure for the preparation of 3-prenyl-2-quinolones involves refluxing a solution of an aromatic amine and diethyl prenylmalonate in diphenyl ether. An interesting study of other products of these reactions has led to the identification of tetracyclic compounds, cf. (31), and 3,3 -methylenebis-2-quinolones, cf. (32) mechanisms for the formation of these compounds were proposed. ... 

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