78008-36-3Relevant academic research and scientific papers
Synthesis of enantiomeric diethyl (1R,2R)- and (1S,2R)-1,2,3- trihydroxypropylphosphonates
Wroblewski, Andrzej E.,Balcerzak, Katarzyna B.
, p. 6833 - 6840 (1998)
Addition of diethyl phosphite to 2,3-O-cyclohexylidene-D-glyceraldehyde catalyzed by triethylamine or fluorides led to ca. 35:65 mixtures of diethyl (1R,2R)- and (1S,2R)-2,3-O-cyclohexytidene-1,2,3-trihydroxypropylphosphonates (4a) and (4b). Application of lithium diethylphosphonate only slightly improved diastereoselectivity. Through chromatographic separation of 4a and 4b the protected trihydroxypropylphosphonates became available for the first time as pure enantiomers. The 1S configuration in the major diastereoisomer 4b was assigned on the basis of conformational and configurational analysis of 1,2-O-isopropylidene derivatives obtained from the title compounds.
Organocatalytic Michael addition to (D)-mannitol-derived enantiopure nitroalkenes: A valuable strategy for the synthesis of densely functionalized chiral molecules
Caruso, Lucia,Puglisi, Alessandra,Gillon, Emmerance,Benaglia, Maurizio
, (2019)
Carbohydrates are abundant renewable resources and are a feedstock for green chemistry and sustainable synthesis of the future. Among the hexoses and the pentoses present in biomass, mannitol was selected in the present project as a valuable platform, directly available from the chiral pool, to build highly functionalized molecules. Starting from (R)-2,3-O-cyclohexylidene glyceraldehyde, which is easily prepared in a large scale from D-mannitol, an enantiopure chiral nitro alkene was prepared by reaction with nitromethane, and its reactivity studied. Organocatalytic Michael addition of dimethyl malonate, β-keto esters, and other nucleophiles on the nitro alkene afforded high stereoselectivity and densely functionalized chiral molecules, which were further synthetically developed, leading to five-membered lactones and bicyclic lactams. Preliminary studies showed that the metal-free catalytic reaction on the chiral nitro alkene can be performed under continuous flow conditions, thus enabling the use of (micro)mesofluidic systems for the preparation of enantiomerically pure organic molecules from the chiral pool.
An efficient synthesis of enantiomerically pure diethyl 2,3-dihydroxypropylphosphonate
Wroblewski, Andrzej E.,Halajewska-Wosik, Anetta
, p. 2075 - 2077 (2004)
A reliable method for the synthesis of the enantiomerically pure diethyl (R)-2,3-dihydroxypropylphosphonate from 1,2;5,6-di-O-cyclohexylidene-D-mannitol is elaborated.
Confirmation of the stereochemistry of two naturally occurring epimeric phenylpropanoids via synthesis: Elucidation of hitherto unknown full stereostructures
Chakraborty, Ipsita,Chatterjee, Sandip,Manna, Avrajit,Bhaumik, Tanurima
, p. 1597 - 1599 (2019)
Herein we report our efforts toward unequivocal assignment of the hitherto unknown absolute configurations of two naturally occurring phenylpropanoids from Abies delavayi and Abies fabri via a combination of chiral pool synthesis and single crystal X-ray
Novel 1,2,3-triazole-tethered Pam3CAG conjugates as potential TLR-2 agonistic vaccine adjuvants
Mhamane, Tukaram B.,Sambyal, Shainy,Vemireddy, Sravanthi,Khan, Imran A.,Shafi, Syed,Halmuthur M., Sampath Kumar
, (2021/04/12)
A focused library of water soluble 1,2,3-triazole tethered glycopeptide conjugates derived from variety of azido-monosaccharides and aliphatic azido-alcohols were synthesized through manipulation at the C-terminus of Pam3CAG and screened for their potential as TLR2 agonistic adjuvants against HBsAg antigen. In vitro ligand induced TLR2 signal activation was observed with all the analogues upon treatment with HEK blue TLR2 cell lines. Conjugate derived from ribose (6e), which exhibited pronounced HBsAg specific antibody (IgG) titer also shown enhanced CD8+ population indicating superior cell mediated immunity compared to standard adjuvant Pam3CSK4. Further, docking studies revealed ligand induced heterodimerization between TLR1 and 2. Overall, the result indicates the usefulness of novel conjugates as potential vaccine adjuvant.
A general and concise stereodivergent chiral pool approach toward trans-(4S,5R)- and cis-(4R,5R)-5-alkyl-4-methyl-γ-butyrolactones: Syntheses of (+)-trans- and (+)-cis-whisky and cognac lactones from D-(+)-mannitol
Manna, Avrajit,Chakraborty, Ipsita,Chatterjee, Sandip,Bhaumik, Tanurima
, (2021/10/12)
A straightforward synthesis of (+)-trans-(4S,5R)- and (+)-cis-(4R,5R)-whisky lactones starting from D-(+)-mannitol has been reported here in fewer number of efficient steps compared to existing literature processes involving D-mannitol as the chiral pool starting material. Chiron approach directly translated chirality of D-mannitol to one of the two chiral centers in these target molecules. Toward this end, stereoisomerically pure trans- and cis-iodomethyl-γ-lactones were formed in the penultimate step. These two acted as versatile advanced common intermediates as they were also converted to the (+)-trans-(4S,5R)- and (+)-cis-(4R,5R)-cognac lactones, respectively. To the best of our knowledge, till date no synthesis of cognac lactones starting from D-mannitol has been reported. All these lactones are identified as the key aroma components of aged alcoholic beverages.
Enantiodivergent syntheses of (+)- and (?)-1-(2,6-dimethylphenoxy)propan-2-ol: A way to access (+)- and (?)-mexiletine from D-(+)-mannitol
Manna, Avrajit,Chatterjee, Sandip,Chakraborty, Ipsita,Bhaumik, Tanurima
, (2020/01/08)
Chiron approach was used to acquire optically pure (R)- and (S)-1-(2,6-dimethylphenoxy)propan-2-ol, immediate precursors of (S)- and (R)-mexiletines, respectively. Two different routes were followed from a D-mannitol-derived optically pure common precursor to get the enantiomeric alcohols separately. Comparison of their specific rotation values with the corresponding literature values as well as exact mirror-image relationship between their CD curves proved their high enantiopurity. These alcohols were then transformed to the corresponding amine-drugs in an efficient one-step process instead of two steps described in the literature.
Synthesis and in vitro biological evaluation of 3-amino-3-deoxydihydrosphingosines and their analogues
Gonda, Jozef,Jáger, Dávid,Kuchár, Juraj,Martinková, Miroslava,Pilátová, Martina Bago,Raschmanová, Jana ?paková
, (2019/12/11)
The stereoselective synthesis of the 3-amino-3-deoxydihydrosphingosines and their isomeric analogues from dimethyl L-tartrate is described by means of [3,3]-sigmatropic rearrangements and the cross metathesis reaction as a cornerstone of the developed str
Synthesis of ABBV-168, a 2′-Bromouridine for the Treatment of Hepatitis C
Voight, Eric A.,Brown, Brian S.,Greszler, Stephen N.,Halvorsen, Geoff T.,Zhao, Gang,Kruger, Albert W.,Hartung, John,Lukin, Kirill A.,Martinez, Steven R.,Moschetta, Eric G.,Tudesco, Michael T.,Ide, Nathan D.
, p. 4723 - 4734 (2018/12/11)
ABBV-168 is a dihalogenated nucleotide under investigation for the treatment of hepatitis C virus. Three synthetic routes aimed at achieving the stereoselective installation of the C2′ gem-Br,F substitution and subsequent Vorbruggen glycosylation were explored to prepare the penultimate nucleoside intermediate. Development culminated in a route to ABBV-168 featuring a de novo chromatography-free furanose synthesis, protecting group-directed Vorbruggen glycosylation, and highly selective phosphoramidation to furnish the API.
Stereodivergent approach to Alzheimer's therapeutic agent (R)-(?) and (S)-(+)-arundic acid employing chiral 4-pentenol derivatives as building blocks
Bhosale, Viraj A.,Waghmode, Suresh B.
, p. 2342 - 2348 (2017/04/03)
An efficient stereodivergent total synthesis of anti-Alzheimer agent (R)-(?) and (S)-(+)-arundic acid has been achieved from both chiral and nonchiral materials. This strategy features an efficient approach to separable diastereomeric C-2 chiral 4-pentenol intermediates employing proline catalysed asymmetric α-aminooxylation and [3,3] sigmatropic Claisen rearrangement are the highlights of present synthesis.
