Total syntheses of oroidin, hymenidin and clathrodin

Abstract

The total syntheses of oroidin, hymenidin and clathrodin are reported via the intermediacy of an imidazo[1,2-a]pyrimidine derivative. The chemistry described herein obviates the need for expensive guanidine reagents, multiply protected prefunctionalized 2-aminoimidazole synthons, or the need for laborious olefinations thereby achieving synthetic efficiency amenable to scale-up. The approach outlined in this manuscript provides an opportunity for further functionalizations through the imidazo[1,2-a]pyrimidine core and through functional groups placed strategically on the side chain.

Towards unbiased and more versatile NMR‐based structure elucidation: A powerful combination of CASE algorithms and DFT calculations

“…Oroidin (C 11 H 10 Br 2 N 4 O), a highly proton-deficient bromopyrrole (5) isolated from the sponge Agelas oroides, has been extensively studied by IR, NMR, and X-ray crystallography and was confirmed by direct synthesis. [21][22][23] When the NMR data of oroidin were analyzed by the ACD/Structure Elucidator, the program generated an output file containing 157 possible structures. After 13 C chemical shift calculations, the four highest ranked structures had very low average and maximum deviations of predicted carbon chemical shifts (see Figure 4), thus prompting the utilization of DFT calculations for further differentiation.…”

Facile synthesis of 3-substituted imidazo[1,2-a]pyridines through formimidamide chemistry

“…Our efforts commenced with the synthesis of N,N-dimethyl-N'-(pyridin-2-yl)formimidamide (1) accessed through reaction between 2-aminopyridine and N,N-dimethylformamide dimethyl acetal (DMF-DMA) under reux in toluene (see Table 1). 14 We initially attempted to access imidazopyridine 3a by exposing compound 1 and benzyl bromide together to elevated temperatures (toluene/115 C in the pressure tube), but we could only isolate the quaternary ammonium salt (2a). We have reasoned that the cyclization of 2a may require the help of an acidic or basic promoter, as the attempted cyclization of 2a even at highly elevated temperature (i.e., 180 C/DMSO) also failed to access compound 3a.…”

“…12 All these methods have certain advantages, as well as disadvantages, such as formation of regioisomeric mixtures, harsh and demanding conditions, need for uncommon reagents or catalysts. Inspired by the lone example reported by Würthwein et al, involving base-mediated 6-electron cyclization of imino pyridinium salt to obtain 2,3-disubstituted imidazopyridine from benzyl bromide and benzaldehyde, 13 and buoyed by our previous success in employing aminopyrimidine formimidamide chemistry, 14 we became interested in extending and furthering the scope of the later functionality to obtain 3substituted imidazopyridines. We reasoned that activating the simple halides through formation of corresponding formimidamide-pyridinium salts and thereby incorporating an electrophilic carbon onto 2-aminopyridine would obviate the need for a-halo ketones as the corresponding 1,2-bis-electrophiles.…”

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

“…Condensation of the resulting diamine 201 with the appropriately substituted aryl aldehydes 36 in refluxing EtOH afforded bis-imines 202a-j. Finally, the [2+2] cycloaddition reaction (wrongly named by the authors as a Staudinger reaction) that involved bis-imines 202a-j and ketene generated in situ from chloroacetyl chloride (151) and Et 3 N provided bisazetidinones 196a-j (Scheme 38) [121].…”

“…On the other hand, a similar reaction sequence involving the [2+2] cycloaddition reaction of bis-imines 196a-j and ketene generated in situ from chloroacetyl chloride (151) and Et 3 N, was employed for the synthesis of imidazole containing bisazetidinones 196a-j in excellent yields (Scheme 39). Bis-imines 203a-j were, in turn, prepared by reaction of 198 with 3-nitrobenzaldehyde (204) in the presence of zeolite under microwave irradiation and selective reduction of the nitro groups of the resulting compound 205 followed by condensation of the appropriate aldehydes 36 with diamine 206 resulting from the reduction reaction (Scheme 39) [121].…”