Guanidines, alkyl amino

The guanidine moiety was incorporated by dimethyl (2,2,5,7,8-pentamethylchromane-6-sulfonyl N-alkylated amino) dithiocarbonate[264] (Pmc-dithiocarbonate) 91 in two steps. One methylsulfanyl group was replaced by the primary amino group of Bzl-Norn-OBzl in the presence of excess DIPEA and the isothiourea obtained was reacted with silver nitrate under basic conditions to yield the intermediate sulfonylcarbodiimide which reacts immediately with ammonia to yield the guanidine Bzl-Narg(Pmc)-OBzl 91. 

Below are some refs to alkyl amino- and aminoalkyl-guanidine s ... 

Scheme 14 shows a typical example in a series of reactions in which a supported amino acid reacted with fluorenylmethoxycarbonyl isothiocyanate to give a supported (on Rink s amide)35 thiourea.36 Removal of the protection followed by 5-alkylation gave supported isothioureas. Reaction of these with amines, then cleavage from the resin, afforded substituted guanidines. For 10 examples the purities were between 40 and 92%. An aryl group separates the resin from the guanidine, just as in the sequences shown in Schemes 11 and 12. 

Di(alkyl or aryl)amino-l,2,4-thiadiazoles (90 R,R = alkyl or aryl) are similarly obtainable in 60-85% yields from the appropriate disubstituted amidinothioureas (89 R,R = alkyl or aryl).56,57 The preparation of the latter from monosubstituted guanidines (87) and isothiocyanate esters (88) might conceivably yield the isomeric ami-... 

Alkylamineguanl dines. See Amino alkyl-guanidines and Alkylaminoguanidlnes... 

The most popular preparations of pyrimido[4, 5 ]pyrimidi nes are based on cyanoethylene or cyanomethylene derivatives. In many of these preparations the appropriate acid chloride (R1 = alkyl, aryl) is reacted with malononitrile to give an enol (250), which is readily alkylated to the enol ether (251). This can be condensed with guanidine or a variety of amidines (R2 = H, alkyl, aryl) to yield the key intermediate 4-amino-5-cyanopyrimidines (252) (81S955). Reaction with a second mole of guanidine or amidine is a convenient preparation of a variety of pyrimido[4,5 ]pyrimidines. Under the appropriate conditions the final ring system can be obtained from the enol ether in one step (68JMC568). 

A complementary approach to (511) and (512) (Scheme 3.101 and 3.102) [53, 216] was patterned after methodology developed in Taylor s laboratories [217,218]. Alkylation of ethyl/>-mercaptobenzoate with the chloromethylpyra-zine (16a) furnished (513). Guanidine cyclization to give (514) followed by saponification resulted in concomitant hydrolysis of the 4-amino group to provide the pteroic acid analogue (509), which was converted to (511) in the usual manner. In order to avoid hydrolysis of the 4-amino group, the initial... 

Lehn synthesised guanidinium-based cationic steroids incorporating an acylhy-drazone linker using the approach shown in Fig. 9 [141]. The synthesis was developed from a polyamine scaffold by guanidination of the primary amino groups and alkylation of the secondary amine with methyl chloroacetate to introduce the ester moiety required to form a hydrazide group by reaction with hydrazine monohydrate. Cationic steroid hydrazones were then prepared via an acetic acid catalysed reaction with cholestanones, which demonstrated high transfection efficiency and low toxicity in a variety of cell lines [141]. 

Another key intermediate for pteridine synthesis was also seen in 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide which reacts with various amines to form the corresponding amides followed by cyclization with triethyl orthoformate giving 3-alkyl-6-phenyl-4(3/7)pteridinone 8-oxides <87JHC1109>. The synthesis of 2,4-diamino-6-methylpteridine 5-oxide (371) was achieved from 5-methyl-pyrazine-2-carboxamide (366) via the 4-oxide (367), a Hofmann degradation (368), bro-mination (369), and cyanation (370) followed by cyclization with guanidine to give (371) (Scheme 60) <93JHC841>. 

Disulfide linkages may be broken either oxidatively or reductively. The former method involves the treatment of the protein with performic add, which converts all disulfide bonds into cysteic add residues. This procedure is usually performed before a protein is hydrolyzed for amino add analysis. Cystine and cysteine are then determined as cysteic add. The reductive cleavage of disulfide bonds involves the treatment of the protein with mercaptoethanol (SH-CH2-CH2-OH), followed by the alkylation of the newly formed -SH groups. The complete disruption of all secondary interactions (that is, complete denaturation) can be achieved in most proteins with 6 M guanidine hydrochloride and 0.1 M mercaptoethanol or 8 M urea and 0.1 M mercaptoethanol. 

The oxidation of the alcohol was performed with supported perruthenate (8.48, Fig. 8.46) to produce clean aldehydes 8.91 after filtration. The Henry reaction was performed in the presence of a commercially available, supported strong base 8.92 and an excess of volatile nitroalkenes, giving clean nitroalcohols 8.93 after filtration and evaporation. The reaction mixtures from the trifluoroacetylation/elimina-tion steps were purified with commercially available amino PS resin 8.58 to scavenge the trifluoroacetates and with acidic ion-exchange resin 8.76 to remove the TEA-derived salts. Again, the nitrostyrenes 8.94 were obtained cleanly after filtration and evaporation. Cycloaddition with isocyanoacetate was promoted by the commercially available, supported guanidine base 8.95, while the subsequent N-alkylation of the pyrroles 8.96 was performed with an excess of halide in the presence of the commercially available, supported phosphazene 8.97. In this case, the excess halide was removed by treatment with supported 8.58, and filtra-... 

---