109208-40-4Relevant articles and documents
Formal synthesis of a 2- and 8-functionalized 1,4,7-trioxa-10-azaspiro[5.5]undecane
Lemaire,Posada,Gourcy,Jeminet
, p. 627 - 629 (1995)
(E,E)-(2R,6S,8R )-(+)-N-Benzoyl-2,8-dihydroxymethyl-1,4,7-trioxa-10-azaspiro[5.5]undec ane was synthesised in seven steps from (S)-isopropylideneglycerol as chiral precursor. The final cyclodehydration reaction was carried out on a dihydroxyamidoketone intermediate.
Mild nonepimerizing N -alkylation of amines by alcohols without transition metals
Guerin, Claire,Bellosta, Veronique,Guillamot, Gerard,Cossy, Janine
supporting information; experimental part, p. 3534 - 3537 (2011/08/10)
A one-pot two-step sequence involving an oxidation/imine-iminium formation/reduction allowed the N-alkylation of amines by alcohols without any epimerization when optically active alcohols and amines are involved in the process.
Third-generation immucillins: Syntheses and bioactivities of acyclic immucillin inhibitors of human purine nucleoside phosphorylase
Clinch, Keith,Evans, Gary B.,Frohlich, Richard F. G.,Furneaux, Richard H.,Kelly, Peter M.,Legentil, Laurent,Murkin, Andrew S.,Li, Lei,Schramm, Vern L.,Tyler, Peter C.,Woolhouse, Anthony D.
body text, p. 1126 - 1143 (2010/02/16)
ImmH (1) and DADMe-ImmH (2) are potent inhibitors of human purine nucleoside phoshorylase (PNP), developed by us and currently in clinical trials for the treatment of a variety of T-cell related diseases. Compounds 1 and 2 were used as templates for the design and synthesis of a series of acyclic immucillin analogues (8-38) in order to identify simplified alternatives to 1 and 2. SerMe-ImmG (8) and DATMe- ImmG (9) displayed the lowest inhibition constants of 2.1 and 3.4 pM, respectively, vs PNP. It was postulated that the flexible natures of 8 and 9 enabled them to adopt conformations resembling those of 1 and 2 within the active site of PNP and that the positioning of two hydroxyl groups was critical for picomolar activity. SerMe-ImmH (10, K d = 5.2 pM) was shown to be orally available in mice with a long biological residence time on blood PNP.
ACYCLIC AMINE INHIBITORS OF NUCLEOSIDE PHOSPHORYLASES AND HYDROLASES
-
Page/Page column 31; 32, (2008/06/13)
The invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNPs) and/or nucleoside hydrolases (NHs). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.
ACYCLIC AMINE INHIBITORS OF 5'-METHYLTHIOADENOSINE PHOSPHORYLASE AND NUCLEOSIDASE
-
Page/Page column 22, (2008/06/13)
The present invention relates to compounds of the general formula (I) which are inhibitors of 5'-methylthioadenosine phosphorylase or 5'-methylthioadenosine nucleosidase. The invention also relates to the use of these compounds in the treatment of diseases or conditions in which it is desirable to inhibit 5'-methylthioadenosine phosphorylase or 5'-methylthioadenosine nucleosidase including cancer, and to pharmaceutical compositions containing the compounds.
Synthesis of glycidol- and sugar-derived bicyclic β- and γ/δ-amino acids for peptidomimetic design
Danieli, Elisa,Trabocchi, Andrea,Menchi, Gloria,Guarna, Antonio
, p. 4372 - 4381 (2007/10/03)
Constrained bicyclic β- and γ/δ-amino acids using glycidol and sugar derivatives were developed. The synthetic strategies involved epoxide ring opening of a glycidol derivative, and subsequent coupling with sugar-derived amines, leading to di- or trisubst
A straightforward synthesis of L-isoserinal
Junquera, Federico,Merchan, Francisco L.,Merino, Pedro,Tejero, Tomas
, p. 7045 - 7052 (2007/10/03)
A convenient preparation of L-isoserinal 3 in six steps and 32.8% overall yield employing D-glyceraldehyde acetonide I as starting material is described. The procedure is inexpensive, easily scaled up and proceeds without observable racemization.
General Method for the Synthesis of Phospholipid Derivatives of 1,2-O-Diacyl-sn-glycerols
Martin, Stephen F.,Josey, John A.,Wong, Yue-Ling,Dean, Daniel W.
, p. 4805 - 4820 (2007/10/02)
An efficient phosphite coupling protocol is described for the syntheses of the major classes of phospholipids that are derived from 1,2-O-diacyl-sn-glycerols and analogues thereof.The symmetrical diacyl glycerols 10c,d were prepared by straightforward acylation of 3-O-benzyl-sn-glycerol (7) with the appropriate carboxylic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP).A simple method for preparing saturated and unstaturated mixed 1,2-O-diacyl-sn-glycerols was then devised that involved stepwise acylation of 7 with different alkyl carboxylic acids and debenzylation; this procedure is exemplified by the preparation of 10a,b.The 1,2-O-diacyl-sn-glycerols 10a-d were then coupled with suitably protected lipid head groups employing reactive alkyl or aryl dichlorophosphites to give intermediate phosphite triesters in high overall yields.Oxidation or sulfurization of these phosphites proceeded smoothly to give the corresponding phosphate or phosphorothioate triesters, deprotection of which then provided the phosphatidylcholines 16 and 17, the phosphatidylethanolamine 20, the phosphatidylserine 28, and the phosphatidylinositols 37 and 38.Preparation of 37 and 38 required the invention of an improved method for resolving the isopropylidene-protected D-myo-inositol derivative 33.This phosphite coupling procedure was modified to assemble phospholipids bearing polyunsaturated acyl side chains at the sn-2-position as exemplified by the preparation of the phosphatidylethanolamine 26.The one-pot phosphite coupling procedure is also applicable to the syntheses of a variety of other biologically interesting phospholipid analogues.For example, the phosphatidylinositol analogues 49-51, in which the hydroxyl group at C(2) of the inositol ring has been modified, were prepared in excellent overall yields by conjoining the 1,2-O-diacyl-sn-glycerol 10c with the protected inositol derivatives 44, 45, and 48.Phospholipid analogues that contain other replacements of the phosphate group including phosphoramidates and thiophosphates may be prepared as evidenced by the syntheses of 56 and 61 in which the sn-3 oxygen atom of the 1,2-O-diacyl-sn-glycerol moiety is replaced with an N-benzyl group or a sulfur atom, respectively.
FACILE SYNTHESIS OF OPTICALLY ACTIVE SULFONATES OF 4-tert-BUTOXYCARBONYL-2-HYDROXYMETHYLMORPHOLINE
Yanagisawa, Hiroaki,Kanazaki, Takuro
, p. 105 - 109 (2007/10/02)
Optically active sulfonates of 4-tert-butoxycarbonyl-2-hydroxymethylmorpholine were prepared from 1,2:5,6-di-O-D-mannitol by practical procedures.These compounds are versatile intermediates for optically active isomers of a number of neuropharmacologicall