81997-76-4

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl (2E,4S)-4,5-isopropylidenedioxy-2-methylpent-2-enoate is used as a key intermediate in the synthesis of 2''-deoxy-2''-fluoro-2''-C-methylcytidine (PSI-6130), a potent and selective inhibitor of Hepatitis C Virus (HCV) NS5B polymerase. This antiviral agent has shown promise in the treatment of Hepatitis C, offering a targeted approach to combat the virus.
Used in Marine Natural Products Synthesis:
(2E)-3-[(4S)-2,2-DiMethyl-1,3-dioxolan-4-yl]-2-Methyl-2-propenoic acid ethyl ester also serves as a valuable building block in the synthesis of marine dolabellane diterpenoids, such as claenone, palominol, and dolabellatrienone. These natural products exhibit a range of biological activities, including anti-inflammatory, antimicrobial, and anticancer properties, making them attractive targets for drug discovery and development.
Used in Antiviral Agent Synthesis:
Due to its unique structure and reactivity, Ethyl (2E,4S)-4,5-isopropylidenedioxy-2-methylpent-2-enoate has potential applications in the synthesis of related antiviral agents. Its ability to be incorporated into various molecular frameworks allows for the exploration of new compounds with potential antiviral activity, further expanding the arsenal of treatments for viral infections.

Upstream product

• 2985-33-3 monoethyl methylmalonate 
• 15186-48-8 2,3-isopropylidene-glyceraldehyde 
• 21382-82-1 (carbethoxyethylidene)triphenylphosphorane 
• 3699-66-9 ethyl 2-diethoxyphosphorylpropionate 
• 1707-77-3 1,2:5,6-di-O-isopropylidene-D-mannitol 
• 22323-80-4 (4S)-2,2-dimethyl-[1,3]dioxolane-4-carbaldehyde 
• 535-11-5 Ethyl 2-bromopropionate 

Downstream Products

• 425427-17-4 (3R,4S,4'S)-2-N-benzyl-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-4-methyl-1,2-isoxazolidin-5-one 
• 93635-76-8 (2S,3R)-3-[(4R)-2,2-dimethyl-[1,3]dioxolane-4-yl]-2,3-dihydroxy-2-methylpropionic acid ethyl ester 
• 1410810-08-0 4-(((1S,2R)-2-(hydroxymethyl)-2-methylcyclopropyl)buta-1,3-diynyl)benzoic acid 
• 1410810-09-1 (S)-methyl 3-(tert-butoxycarbonylamino)-2-(4-(((1S,2R)-2-(hydroxymethyl)-2-methylcyclopropyl)buta-1,3-diynyl)benzamido)-3-methylbutanoate 
• 1410809-52-7 N-((S)-3-amino-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-(((1S,2R)-2-(hydroxymethyl)-2-methylcyclopropyl)buta-1,3-diynyl)benzamide trifluoroacetate 
• 879551-01-6 (4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-meth-yl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide 
• 879551-04-9 (3R,4R,5R)-3?fluoro?4?hydroxy?5?(hydroxymethyl)?3?methyltetrahydrofuran?2?one 
• 874638-80-9 ((2R,3R,4R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate 
• 93636-26-1 ethyl 4,5-O-isopropylidene-2-C-methyl-D-xylonate 
• 93635-77-9 C₂₇H₂₂O₈ 

Relevant academic research and scientific papers

Enantioselective divergent syntheses of several polyhalogenated plocamium monoterpenes and evaluation of their selectivity for solid tumors

The family of polyhalogenated monoterpenes from Plocamium counts over a hundred known members. Using glyceraldehyde acetonide as a chiral-pool precursor, an enantioselective and divergent strategy was developed that provides a blueprint for the synthesis of many of the small yet complex acyclic members of this family. The broad applicability of this approach is demonstrated with the short, eight-step synthesis of four natural products and three analogues. These syntheses are the first of any members of the acyclic polyhalogenated Plocamium monoterpenes and permitted the evaluation of their selectivity against a range of tumor cell lines. Glyceraldehyde acetonide serves as a chiral glyoxal equivalent and a linchpin for the enantioselective synthesis of several acyclic polyhalogenated monoterpenes from the red algae Plocamium. Several of these compounds demonstrate selective toxicity towards solid-tumor cell lines over leukemia cell lines, as well as low-micromolar cytotoxicity towards the HCT-116 human colon carcinoma cell line.

Preparation method of 2-C-methyl-4, 5-O-(1-methylvinyl)-D-arabitic acid ethyl ester

The invention discloses a preparation method of 2-C-methyl-4, 5-O-(1-methylvinyl)-D-arabitic acid ethyl ester (formula I). Compared with the prior art, the preparation method has short reaction steps,reduces the use of organic solvents and generation of solid waste. At the same time, the used reagents are all conventional reagents, the method has the characteristics of simple operation, mild reaction conditions and environmental friendliness, and can achieve industrial preparation of 2-C-methyl-4, 5-O-(1-methylvinyl)-D-arabitic acid ethyl ester.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.

A Synthesis of (-)-(R)- and (+)-(S)-Lavandulol, (+)-Lavandulyl 2-methylbutanoate, and (+)-lavandulyl senecioate through orthoester johnson-claisen rearrangement

An efficient synthesis of (-)-(R)- and (+)-(S)-lavandulol, (+)-lavandulyl 2-methylbutanoate and (+)-lavandulyl senecioate is presented in this paper. The synthetic strategy features a chiral-pool approach to an allyl alcohol intermediate, and an orthoester Johnson-Claisen rearrangement as the key step. An efficient synthesis of (-)-(R)- and (+)-(S)-lavandulol, (+)-lavandulyl 2-methylbutanoate and (+)-lavandulyl senecioate is presented. The synthetic strategy features a chiral-pool approach to an allyl alcohol intermediate, and an orthoester Johnson-Claisen rearrangement as the key step. Copyright

HYDROXAMIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT OF BACTERIAL INFECTIONS

Antibacterial compounds of Formula I are provided: as well as stereoisomers and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; use of such compounds in the treatment of bacterial infections and processes for the preparation of such compounds.

An efficient and diastereoselective synthesis of PSI-6130: A clinically efficacious inhibitor of HCV NS5B polymerase

(Chemical Equation Presented) R7128 is the prodrug of 2′-deoxy- 2′-fluoro-2′-C-methylcytidine (PSI-6130), a potent and selective inhibitor of HCV NS5B polymerase. Currently, R7128 is in clinical trials for the treatment of HCV infection. To support clinical development efforts, we needed an efficient and scalable synthesis of PSI-6130. We describe an improved, diastereoselective synthetic route starting with protected D-glyceraldehyde. No chiral reagents or catalysts were used to produce the three new contiguous stereocenters. Introduction of fluorine at the C-2 tertiary carbon was accomplished in a highly regio- and stereoselective manner through nucleophilic substitution on a cyclic sulfate. Scale-limiting chromatographic purifications were eliminated through the use of crystalline intermediates.

Spongipyran synthetic studies. Total synthesis of (+)-spongistatin 2

Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a CaII ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equatorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of CaII ion to furnish (+)-spongistatin 2 (2). The synthesis proceeded with a longest linear sequence of 41 steps.

PREPARATION OF 2'-FLUORO-2'- ALKYL- SUBSTITUTED OR OTHER OPTIONALLY SUBSTITUTED RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES

The present invention provides (i) processes for preparing a 2'-deoxy-2'-fluoro-2'-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2'-deoxy-2'-fluoro-2'-C--methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally--occurring, nucleoside.

Selective conjugate addition of nitromethane to enoates derived from D-mannitol and L-tartaric acid

The conjugate addition of nitromethane to enoates prepared from D-(+)-mannitol, substituted at the α-position by a methyl or a benzyl group, was investigated. While excellent syn-selectivity (d.e. >90%) was obtained from α-benzyl enoates (used as a mixture of epimers, E/Z=1.8:1), for α-methyl enoates the selectivity depended on the stereochemistry of the double bond in the acceptor (d.e. >90% for the (Z)-enoate and 50% for the (E)-enoate). In all cases, a mixture of epimers was formed at the newly generated stereocenter at the α-position. The epimeric syn-adducts were transformed into the corresponding pure α,β,γ-trisubstituted γ-butyrolactones by cyclization in acid medium followed by epimerization of the stereocenter at the α-position in DBU/CH2Cl2. When enoates derived from L-tartaric acid were used as acceptors, syn-selective conjugate additions were also observed (d.e. >90% for the (Z)-isomer and 50% for the (E)-isomer). The configuration at the newly generated stereogenic centers were assigned based on X-ray analyses, 1H-1H coupling constants and NOE experiments in NMR spectroscopy.

Synthesis of novel 3'-C-methyl-apionucleosides: An asymmetric construction of a quaternary carbon by claisen rearrangement

The synthesis of 2,3-dideoxy-3-C-(hydroxymethyl)-3-C-glycero-tetrofuranosyl nucleosides was accomplished in high enatiomeric purity (98.5% ee) via [3,3]-sigmatropic Claisen rearrangement of (E)(S)-5-benzyloxy-1-tert-butyldimethylsilanyloxy-4-methyl-pent-3 -en-2-ol prepared from 2,3-O-isopropylidene-D-glyceraldehyde. The synthesized nucleosides were assayed against human immunodeficiency virus (HIV) and hepatitis B virus in human peripheral blood mononuclear (PBM) and 2.2.15 cells, respectively. 6-Amino-9-[2,3-dideoxy-3-C-(hydroxymethyl)-3-C-methyl-β-D-glycer o-tetrofuranosyl]-2-fluoropurine shows moderate antiviral activity (EC50 = 2.55 μM) against HIV-1 strains and 6-amino-9-[3-deoxy-3-C-(hydroxymethyl)-3-methyl-α-D-glycero-tetr ofuranosyl]-2-fluoropurine exhibits potent anti-HIV activity EC50 = 0.073 μM) with significant cytotoxity (IC50 = 1.0 μM). (C) 2000 Elsevier Science Ltd.