2-Guanidino

D, J Sturzebecher and WBode 1991. Geometry of Binding of the N-Alpha-Tosylated Piperidides of weffl-Amidino-Phenylalanine, Para Amidino-Phenylalanine and para-Guanidino-Phenylalanine to Thrombin and Trypsin - X-ray Crystal Structures of Their Trypsin Complexes and Modeling of their Thrombin Complexes. FEBS Letters 287 133-138. 

N-(2-Thiazolyl)cyanamide may be converted into guanidino derivatives by the action of hydrazines (487). /V-Aryl-N -(4-aryl-2-thiazolybguanidines... 

Creatine (HjO) (V-guanidino-V-methylglycine) [6020-87-7] M 131.1, m 303°, pK 2.63, pKj 14.3. Likely impurities are creatinine and other guanidino compounds. Crystd from water as monohydrate. Dried under vacuum over P2O5 to give anhydrous material. 

Dihydrostreptomycin sesquisulfate [5490-27-7] M 461.4, m 250 (dec), 255-265 (dec), [a]p -92.4 (c 1, H2O), pKgsJd)-- 9.5 (NMe), pKes,(2,3) 13.4 (guanidino). It crystallises from H2O with MeOH, -BuOH or methyl ethyl ketone. The crystals are not hygroscopic like the amorphous powder, however both forms are soluble in H2O but the amorphous solid is about 10 times more soluble than the crystals. The free base also crystallises from H20-Me2C0 and has [a]p -92° (aqueous solution pH 7.0). [Solomons and Regina Science 109 515 7949 Wolf et al. Science 109 515 7949 McGilveray and Rinehart J Am Chem Soc 87 4003 1956]. 

The guanidine-type resonance, which is present in aliphatic guanidines, is stronger than that in the corresponding amidines, at least in the case of the cationic forms. 2-Aminopteridine and 2-aminoquinazoline cations are two examples of compounds in which hydration is stabilized by the presence of a guanidino group (32). 

Treatment of 3-amino-4-oxoquinazolines (9) with cyanamide gave the 2-amino-l,2,4-triazolo [l,5-c]quinazolines 11 as a result of cyclodehydration of the intermediate 3-guanidino-4-oxoquinazolines 10 (68CB2106) (Scheme 9). Similarly, reaction of the 3-amino-4-thioxoquinazoline 12 with alkyl or aryl isothiocyanates yielded the mesoionic l,2,4-triazolo[l,5-cjquinazolines 14 (84S881) (Scheme 10). 

The association of a specific pharmacologic activity with certain functionality was remarked on earlier. The guanidino group, for example, often yields compounds that show hypotensive activity because of peripheral sympathetic blockade (see, for example, bethanidine). Attachment of a piperidine group to the side chain proves compatible with retention of this activity. 

The Diels-Alder reaction of nitroalkenes with Danishefsky s dienes is applied to synthesis of truncated carbocyclic analogues of a potent neuraminidase inhibitor 4-guanidino-NemAc en fsee Scheme 8.5. Carbocyclic analogs are found to retain interesting levels of antiviral activity comparable to those shovm by their oxygen-containing compounds in Scheme 8.5. 

Arginine, the most basic of the 20 common amino acids, contains a guanidino functional group in its side chain. Explain, using resonance structures to show how the protonated guanidino group is stabilized. 

S,3R)-Aziridine-2-carboxylic amide 258 (Scheme 3.95) has been used in the synthesis of the cyclic guanidino amino acid, L-epicapreomycidine (260) [145]. Treatment of 258 with saturated ammonia in methanol at 30 °C for 4 days in a pressure bottle resulted in the aziridine ring-opening product, which afforded 259 in 52 % yield after removal of the Cbz protecting group. 

Evidently, the titratable functions of M are two very strong bases, since the equivalent weight of M calculated from the curve was 391, corresponding to approximately half the molecular weight (791) calculated from the analyses discussed above. Apparently, one of the functions was due to the guanidino group of the isolated... 

Bei der Reduktion von Purinen wird zumeist der Funfring aufgespalten. Die galvano-statische Elektrolyse (3—4 A/8 V fur mehrere Stdn.) von 2,8-Diamino-purin in 25,8 n Schwefelsaure an Blei-Kathoden liefert neben 2,8-Diamino-1,2,3,4,5,6-hexahydro-9H-purin 2-Amino-5-guanidino-6-oxo-3,4,5,6-tetrahydro- und 2-Amino-5-guanidino-3,4-dihydro-pyrimidin (nur das Tetrahydro-pyrimidin-Derivat ist abtrennbar (Totalausbeute -45% d.Th.)3. 

GlaxoWellcome (now GlaxoSmithKline) licensed 4-deoxy-4-guanidino-Neu5Ac2en 12 as a lead drug candidate under the generic name zanamivir and... 

Fig. 5 Key interactions of 4-deoxy-4-guanidino-Neu5Ac2en (zanamivir) 12 with the active site of influenza A virus sialidase [Figure generated from crystal strucmre data (PDB - Innc) using LIGPLOT (Wallace et al. 1995)]. To the right is shown zanamivir 12 in the same orientation...

Importantly, the crystal structure of 34 complexed with N9 sialidase (Fig. 8) indicated differences in the orientation of the guanidino group in subsite S2, and in its interaction with the active site residues, compared to that of zanamivir (Babu et al. 2000). These differences have implications for cross-reactivity of 34 with zanamivir-resistant influenza viruses that have Glul 19 mutations in the sialidase S2 subsite (see Sect. 5.1). 

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