4255-35-0Relevant academic research and scientific papers
Novel High Energy Intermediate Analogues with Triazasterol-related Structures as Inhibitors of the Ergosterol Biosynthesis V [1]. Synthesis of Hexahydro-5H-imidazo[1′,2′:1,2]pyrimido-[4,3-a]isoquinolines and 1-Alkyl Analogues Representing New 8,13,15-Triazasteroids
Goessnitzer, Edith,Punkenhofer, Asbjoern
, p. 1271 - 1282 (2003)
The synthesis of 1,2,6,10b,11,12-hexahydro-5H-imidazo[1′,2′:1, 2]pyrimido[4,3-a]isoquinolines representing new types of 8,13,15-triazasteroids is described. The tetracyclic title compounds were prepared from 4-(2-hydroxyalkylamino)tetrahydro-2H-pyrimidoisoquinolines, which furnish after conversion to the corresponding bromoalkylamino compounds and base-catalyzed intramolecular nucleophilic displacement cyclization of the latter the desired 1-substituted 8,13,15-triazasteroids with aromatic ring A. The structures of the compounds were proved and assigned on the basis of homo- and heteronuclear correlated 1D and 2D NMR experiments. The title compounds represent triaza-analogues of selected high energy intermediates (HEI) of steroidal substrates formed during the enzymatic transformation of squalene into ergosterol and are designed to act as inhibitory mimicries of HEIs and potential antimycotics.
A waste-minimized protocol for the preparation of 1,2-azido alcohols and 1,2-amino alcohols
Ballerini, Eleonora,Crotti, Paolo,Frau, Ileana,Lanari, Daniela,Pizzo, Ferdinando,Vaccaro, Luigi
supporting information, p. 2394 - 2400 (2013/09/12)
Under solvent-free conditions the reaction of epoxides 1a-i with trimethylsilylazide (2) catalyzed by polystiryl-supported fluoride (PS-DABCOF2) has led to the efficient preparation of the corresponding O-TMS protected 1,2-azido alcohols 3a-i that, by treatment with Dowex-H, gave the related 1,2-azido alcohols 4a-i in excellent yields (83-99% and 82-96%, respectively). The use of a flow procedure has allowed us to significantly minimize waste in the preparation of representative 1,2-azido alcohols 4a, 4c and 4i that have been obtained with E-factors of 1.6, 2.1, and 1.9, respectively. The 1,2-amino alcohols 5a, 5c and 5f have been also prepared, in quantitative yields, by reduction of the corresponding O-TMS protected 1,2-azido alcohols 3a, 3c, and 3f by Pd on the Al2O3/HCOOH system.
Formation of potentially prebiotic amphiphiles by reaction of β-hydroxy-n-alkylamines with cyclotriphosphate
Mullen, Lee B.,Sutherland, John D.
, p. 4166 - 4168 (2008/03/11)
(Chemical Equation Presented) The long and the short of it: In water, long-chain β-hydroxy-n-alkylamines are converted to their O-monophosphates by reaction with cyclotriphosphate. With short-chain pVhydroxy-n-alkylamines, N-triphosphates are formed instead. The difference results from the formation of surfactant assemblies from the long-chain compounds. This surfactant control of reactivity may be of relevance to the prebiotic formation of amphiphiles. P: phosphate unit.
Cobalt(II) chloride-catalyzed chemoselective sodium borohydride reduction of azides in water
Fringuelli, Francesco,Pizzo, Ferdinando,Vaccaro, Luigi
, p. 646 - 650 (2007/10/03)
Reduction of azides to amines and amides was carried out with NaBH4/CoCl2·6H2O in sole water at 25 °C under catalytic heterogeneous conditions. A broad spectrum of azides was reduced in a short time, chemoselectively in high yield and purity.
The synthesis of potent marcocyclic renin inhibitors
Dhanoa, Daljit S.,Parsons, William H.,Greenlee, William J.,Patchett, Arthur A.
, p. 1725 - 1728 (2007/10/02)
An efficient synthesis of a novel class of potent macrocylic renin inhibitors exemplified by compounds 1 and 2, which involves the marcocyclization of 8 and 9 as the key step, is described. The macrocyclic design of renin inhibitors 1 and 2 disclosed here
Efficient Asymmetric Reduction of Acyl Cyanides with B-3-Pinanyl-9-BBN (Alpine-Borane)
Midland, M. Mark,Lee, Penny E.
, p. 3237 - 3239 (2007/10/02)
Acyl cyanides are effectively reduced to optically active β-amino alcohols by using Alpine-Borane followed by sodium borohydride/cobaltous chloride
Importance of the Aromatic Ring in Andrenergic Amines. 5. Nonaromatic Analogues of Phenylethanolamine as Inhibitors of Phenylethanolamine N-Methyltransferase: Role of Hydrophobic and Steric Interactions
Vincek, William C.,Aldrich, Constance S.,Borchardt, Ronald T.,Grunewald, Gary L.
, p. 7 - 12 (2007/10/02)
The synthesis of five classes of nonaromatic analogues of β-phenylethanolamine and an evaluation of their inhibitory potency (IC50) for phenylethanolamine N-methyltransferase (PNMT) are described.The key intermediates for the synthesis of the ethanolamines were the appropriate aldehydes or ketones.The aldehydes 11a (cyclobutyl) and 13a (cycloheptyl) of type A were prepared from the correspondingacids by reduction of the acid to the alcohol with lithium aluminum hydride and oxidation of the alcohol to the aldehyde with pyridinium chlorochromate (PCC).The aldehydes 15a (cycloundecyl) and 41a (adamantyl) of type A were prepared by oxidation of the corresponding alcohols with PCC.The first reported synthesis of cyclononanecarboxaldehyde (type A, 14a) is described.This aldehyde was prepared via a multistep route beginning with a Favorskii rearrangement of 2-bromocyclodecanone to cyclononanecarboxylic acid.The acid was reduced with lithium aluminum hydride to the corresponding alcohol, which was subsequently oxidized to the aldehyde with PCC.The aldehydes or ketones were converted (with trimethylsilyl cyanide) into their cyanohydrin ethers, which were subsequently reduced to the desired ethanolamine with lithium aluminum hydride.The ethanolamines were tested as inhibitors (LCEC assay) of PNMT.The most potent inhibitors were the type A compounds 8 (cyclooctyl), 13c (cycloheptyl), 14c (cyclononyl), and 15c (cycloundecyl) and the type D compounds 26c (cyclononyl) and 27c (cycloundecyl) with IC50 values from 6 to 17 μM.It isconcluded that the binding site of PNMT accepts hydrophobic groups of an optimal length (ca. 6.4 Angstroem) and width (ca. 2.5 Angstroem) and has a significant height restriction for the hydrophobic group.The ethanolamine side chain prefers to lie away from and in the longitudinal axis of the hydrophobic group.An ethanolamine side chain attached to a cycloalkyl ring of n carbon atoms (types A and D) is almost always considerably more potent at inhibiting PNMT than the open-chain compounds of n total carbon atoms (types B, C, and E).
