57323-06-5Relevant articles and documents
Synthesis and Enzymatic Studies of Isoprenoid Thiolo Bisubstrate Analogues
Ramamoorthy, Gurusankar,Phan, Richard M.,Poulter, C. Dale
, p. 5093 - 5100 (2016)
Chain elongation prenyltransferases catalyze the addition of the hydrocarbon moiety of allylic isoprenoid diphosphates to the carbon-carbon double bond in isopentenyl diphosphate (IPP) in the primary building reactions in the isoprenoid biosynthetic pathway. Bis-O-diphosphate analogues 3-OPP/OPP, 4-OPP/OPP, and 5-OPP/OPP and bis-thiolodiphosphate bisubstrate analogues 3-SPP/SPP, 4-SPP/SPP, and 5-SPP/SPP were synthesized. The analogues 4-OPP/OPP, 5-OPP/OPP, 4-SPP/SPP, and 5-SPP/SPP were excellent competitive inhibitors of avian farnesyl diphosphate synthase with KI = 1.0 ± 0.12 μM, KI = 0.5 ± 0.2 μM, KI = 0.7 ± 0.3 μM, and KI = 2.9 ± 0.27 μM, respectively, whereas, analogues 3-OPP/OPP and 3-SPP/SPP displayed mixed type inhibition with KI = 1.4 μM and KI = 5.5 μM, respectively.
Synthesis of 1,2-Dihydropyridines, 2,3-Dihydro-4(1H)-pyridinone, and 1,2,3,4-Tetrahydropyridines via N-Acyl N,O-Hemiacetal Formation
Roduit, Jean-Paul,Wyler, Hugo
, p. 403 - 414 (1985)
New procedures are described for the synthesis of α,β-ethylenic and acetylenic aldehydes from 2-butene- and 2-butyne-1,4-diol, respectively (see Scheme 1).These are applied to the preparation of a particular δ-acetylamino-α,β-ethylenic aldehyde ((E)-5) as well as of its acetylenic analogue 15.On heating in the presence of a silyl enol ether, the former undergoes a complete dehydrative cyclization affording the N-acetyl-1,2-dihydropyridine 19.The addition of HCl to aldehyde (E)-5 results in the production of the 4-chloro-1,2,3,4-tetrahydropyridine 22 which is hydrolyzed to the corresponding alcohol 23 on silica gel.Similarly, the addition of HCl or HBr to the δ-acetylamino-α,β-acetylenic aldehyde 15 leads to the previously unknown 4-halo-1,2-dihydropyridines 26; these are easily hydrolyzed to the 2,3-dihydro-4(1H)-pyridinone 27.The ring-forming process involves a N-acyl N,O-hemiacetal as intermediate which is eventually dehydrated.
Total synthesis and antibacterial testing of the A54556 cyclic acyldepsipeptides isolated from streptomyces hawaiiensis
Goodreid, Jordan D.,Wong, Keith,Leung, Elisa,McCaw, Shannon E.,Gray-Owen, Scott D.,Lough, Alan,Houry, Walid A.,Batey, Robert A.
supporting information, p. 2170 - 2181 (2014/12/11)
The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.
