Studies of the H–D exchange mechanism of malonganenone B

Abstract

Malonganenone B (1) exhibits an unusual H-D exchange of a formyl proton when in deuteric-NMR solvents. Synthetic and kinetic investigations were made to probe the mechanism of this exchange, which appears to occur via an uncommon and transient amine-amide NHC intermediate.

Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products

“…The 1 H NMR spectra of the formamide-(73-77) and N-methyl formamide (78-80) series suggested a mixture of two rotamers, with doubling of most resonances near the head group. These observations are consistent with previous data reported for geranyl formamide [43] and of more relevance, malonganenone B [37]. Conversely, the acetamide analogues (81-85) were not rotameric but became so upon N-methylation (86-88), analogous to DMF.…”

“…The other two purinones selected were 2-mercapto-3-methylhypoxanthine ( 25) and 1,3-dimethyluric acid (26). Alkylation of the methyl series of purinones, and 25, all yielded N-7 monoalkylated regioisomers (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), except for 22, which only yielded N-3,N-7 dialkylated species (27,28) (Scheme 2).…”

“…Conversely, the acetamide analogues (81-85) were not rotameric but became so upon N-methylation (86-88), analogous to DMF. Malonganenones C, H, and K, have a simple formamide head group and analogues were synthesized by formylation [37,38] or acetylation [39,40] of prenyl amines [41], followed by methylation [42] (Scheme 10). The 1 H NMR spectra of the formamide-(73-77) and N-methyl formamide (78-80) series suggested a mixture of two rotamers, with doubling of most resonances near the head group.…”

“…No general trends can be derived from the identity of the head group, but small changes such as methylation seem to have a large effect on activity. For example, 3-methylxanthine ( 23) and theophylline ( 24) differ by the presence of an N-1 methyl and while all side chain lengths of the N-7 alkylated 3-methylxanthines (29)(30)(31)(32)(33) are active, only the N-7 geranylgeranyl theophyllines (36,37) display activity. Converse to N-methyl deactivation, the acetamides are all more active than the formamides by 5-to 13-fold (74 vs. 82, 76 vs. 84, 77 vs. 85).…”

Electrochemical Transformations of Methylxanthines in Non‐Aqueous Medium

“…Noteworthy, compound 5 was not obtained under classical chemical conditions: in fact, in the electrochemical route the formylation occurred at the exocyclic amide nitrogen atom, while in the non‐electrochemical route at the exocyclic amine nitrogen atom (Scheme 3). [17] Thus, the cathodic reduction of the bio‐based 1 in aprotic medium provided the highly amino‐functionalized imidazole 5 , which can find valuable applications as starting material in the synthesis of enamides and related compounds.…”