2834-00-6

Upstream product

• 6089-04-9 3-(tetrahydropyran-2'-yloxy)propyne 
• 143-15-7 1-dodecylbromide 
• 112-53-8 1-dodecyl alcohol 
• 4292-19-7 1-Iodododecane 
• 107-19-7 propargyl alcohol 
• 50-00-0 formaldehyd 
• 765-10-6 1-tetradecyne 

Downstream Products

• 152124-15-7 tert-Butyl-dimethyl-(4-pentadec-2-ynyloxymethyl-benzyloxy)-silane 
• 1026390-93-1 1-Iodomethyl-4-pentadec-2-ynyloxymethyl-benzene 
• 152124-16-8 4-(2-Pentadecynyloxymethyl)phenylmethanol 
• 152124-17-9 tert-Butyl 3-[4-(2-Pentadecynyloxymethyl) phenyl]propanoate 
• 1416322-23-0 C₂₂H₃₄O₃S 
• 75736-52-6 [16,16,16-2H₃]-hexadecanol 
• 1235543-85-7 1-[(tert-butyldiphenylsilyl)oxy]pentadec-15-yne 
• 6064-48-8 1-hydroxy-2(E)-pentadecene 

Relevant academic research and scientific papers

NUCLEOSIDE PRODRUGS AND USES RELATED THERETO

Disclosed are acyclic nucleoside prodrugs with improved metabolic stability and oral bioavailability. In general, the prodrugs are derivatives of acyclic nucleoside phosphonates containing a lipid-like moiety that can increase oral absorption and subsequent stability in the liver and plasma. Preferably, the lipid-like moiety can resist enzyme-mediated ω-oxidation, such as ω -oxidation catalyzed by cytochrome P450 enzymes. Also disclosed are pharmaceutical formulations of the acyclic nucleoside prodrugs. The acyclic nucleoside prodrugs and pharmaceutical formulations thereof can be used to treat viral infections, such as HIV infections, and/or viral-associated cancer, such as HPV-associated cancers.

ω-Functionalized Lipid Prodrugs of HIV NtRTI Tenofovir with Enhanced Pharmacokinetic Properties

Tenofovir (TFV) is the cornerstone nucleotide reverse transcriptase inhibitor (NtRTI) in many combination antiretroviral therapies prescribed to patients living with HIV/AIDS. Due to poor cell permeability and oral bioavailability, TFV is administered as one of two FDA-approved prodrugs, both of which metabolize prematurely in the liver and/or plasma. This premature prodrug processing depletes significant fractions of each oral dose and causes toxicity in kidney, bone, and liver with chronic administration. Although TFV exalidex (TXL), a phospholipid-derived prodrug of TFV, was designed to address this issue, clinical pharmacokinetic studies indicated substantial hepatic extraction, redirecting clinical development of TXL toward HBV. To circumvent this metabolic liability, we synthesized and evaluated ω-functionalized TXL analogues with dramatically improved hepatic stability. This effort led to the identification of compounds 21 and 23, which exhibited substantially longer t1/2 values than TXL in human liver microsomes, potent anti-HIV activity in vitro, and enhanced pharmacokinetic properties in vivo.

Catalytic Access to Functionalized Allylic gem-Difluorides via Fluorinative Meyer–Schuster-Like Rearrangement

An unprecedented approach for efficient synthesis of functionalized allylic gem-difluorides via catalytic fluorinative Meyer–Schuster-like rearrangement is disclosed. This transformation proceeded with readily accessible propargylic fluorides, and low-cost B–F reagents and electrophilic reagents by sulfide catalysis. A series of iodinated, brominated, and trifluoromethylthiolated allylic gem-difluorides that were difficult to access by other methods were facilely produced with a wide range of functional groups. Importantly, the obtained iodinated products could be incorporated into different drugs and natural products, and could be expediently converted into many other valuable gem-difluoroalkyl molecules as well. Mechanistic studies revealed that this reaction went through a regioselective fluorination of alkynes followed by a formal 1,3-fluorine migration under the assistance of the B–F reagents to give the desired products.

Enantioselective Rhodium-Catalyzed Atom-Economical Macrolactonization

A highly attractive route toward macrolactones, which form the cyclic scaffold of a multitude of diverse natural compounds, is described. Although many chemical approaches to this structural motif have been explored, an asymmetric variant of the cyclization is unprecedented. Herein we present an enantioselective macrolactonization through an intramolecular atom-economical rhodium-catalyzed coupling of ω-allenyl-substituted carboxylic acids. The use of a modified diop ligand, chiral DTBM-diop, led to high enantioselectivity (up to 93 % ee). The reaction tolerated a large variety of functionalities, including α,β-unsaturated carboxylic acids and depsipeptides, and provided the desired macrocycles with very high enantio- and diastereoselectivity.

Total synthesis and reassignment of the structures of the antimicrobial lipodepsipeptides circulocin γ and δ

The structures of the naturally occurring antimicrobial lipodepsipeptides circulocin γ and circulocin δ have been reported to comprise a common cyclic depsipeptide core attached to 3-hydroxy,ω-guanidino fatty acid chains differing in length by two methyle

Extended structural modulation of bio-inspired chiral lipidic alkynylcarbinols as antitumor pharmacophores

The chiral alkynylcarbinol motif typically found in natural marine products, has been the subject of intense research activity for its pharmacophoric properties, in particular cytotoxicity against tumor cell lines. In a chemical synthesis-driven four-parameter structure-activity relationship (SAR) study from the (S,E)-eicos-4-en-1-yl-3-ol natural reference 1, the (S)-dialkynylcarbinol unit of the non-natural dehydro derivative 2 emerged as an unprecedented anti-tumoral pharmacophore. An extended study of lipidic alkynylcarbinol pharmacophores is presented, addressing additional structural parameters: Z→E isomerization of the alkenyl carbinol substituent of 1, variation of the lipidic chain length of 2 (C3n, n=3, 4, 6), oxidation or substitution of the carbinol unit of 2 (to ketone, tertiary methylcarbinol, or methylether), cyclomethylenation of the double bond of 1. The synthesis of these analogues is described, including the preparation of enantio-enriched chiral alkynylcarbinol derivatives using a modified Carreira procedure for Zn-mediated addition of (trialkylsilyl)acetylene substrates to ynals in the presence of (-)- or (+)-N-methylephedrine. Preliminary cytotoxicity evaluation of 12 new products against the HCT 116 tumor cell line are finally reported and the results compared with those obtained for 1 and 2. These observations support and refine the relevance of the pharmacophoric character of secondary DAC units.

Ultralow adhesion and friction of fluoro-hydro alkyne-derived self-assembled monolayers on H-terminated Si(111)

New fluorine-containing terminal alkynes were synthesized and self-assembled onto Si(111) substrates to obtain fluorine-containing organic monolayers. The monolayers were analyzed in detail by ellipsometry, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS), static water contact angle measurements (CA), and atomic force microscopy (AFM). The SAMs exhibit excellent hydrophobicity, with static water contact angles of up to 119 and low critical surface tensions of 5-20 mN/m depending on the number of F atoms per molecule. IRRAS confirmed the formation of highly ordered monolayers, as indicated by the antisymmetric and symmetric stretching vibrations of the CH2 moieties at 2918-2920 and 2850-2851 cm-1, respectively. Upon increasing the number of fluorine atoms in the alkyne chains from 0 to 17, the adhesion of bare silica probes to the SAMs in air decreases from 11.6 ± 0.20 mJ/m 2 for fluorine-free (F0) alkyne monolayers to as low as 3.2 ± 0.03 mJ/m2 for a heptadecafluoro-hexadecyne (F17)-based monolayer. Likewise, the friction coefficient decreases from 5.7 × 10-2 to 1.2 × 10-2. The combination of high ordering, excellent hydrophobicity, low adhesion, and low friction makes these fluoro-hydro alkyne-derived monolayers highly promising candidates for use in high-performance microelectronic devices.

17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues

17(R),18(S)-Epoxyeicosatetraenoic acid [17(R),18(S)-EETeTr], a cytochrome P450 epoxygenase metabolite of eicosapentaenoic acid (EPA), exerts negative chronotropic effects and protects neonatal rat cardiomyocytes against Ca 2+-overload with EC50 ≈ 1-2 nM. Structure-activity studies revealed that a cis-Δ11,12- or Δ14,15- olefin and a 17(R),18(S)-epoxide are minimal structural elements for antiarrhythmic activity whereas antagonist activity was often associated with the combination of a Δ14,15-olefin and a 17(S),18(R)-epoxide. Compared with natural material, the agonist and antagonist analogues are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates.

HETEROCYCLIC DERIVATIVES THAT ARE USED IN THE TREATMENT OF NEURODEGENERATIVE DISEASES

The present invention relates to compounds of Formula (I) below, to their pharmaceutically acceptable salts and to their isomers or mixtures of isomers: HetAr—X—CHR1R2 (I) in which: -HetAr represents a group chosen from: —X represents a linear, saturated or unsaturated, hydrocarbon-based chain comprising from 8 to 22 carbon atoms, optionally interrupted by an —NH— or —NH—CO— group, —R1 represents a hydrogen atom or an —OH, —O(C1-C6)alkyl, —OCO((C1-C6)alkyl), —OSO2((C1-C6)alkyl) or —OSO3H group, and —R2 represents a hydrogen atom or a (C2-C6)alkynyl, (C2-C6)alkenyl or (C3-C6)cycloalkyl group. The present invention also relates to a process for preparing the compounds of Formula (I), and also to the use thereof, especially in the treatment of neurodegenerative diseases.

Synthesis of novel symmetrical, single-chain, diacetylene-modified bolaamphiphiles with different alkyl chain lengths

General syntheses of novel symmetrical, single-chain, diacetylene-modified bolaphospholipids have been carried out in five steps. For the ω-alkynols, which have an important role as key intermediates, three different synthetic approaches were comprehensively investigated. For the final synthesis it is suggested that (1) alkylation of lithium (trimethylsilyl)acetylide with tetrahydropyranyl-protected ω-bromoalcohols, followed by (2) cleavage of the trimethylsilyl moiety and the tetrahydropyranyl protecting group, and (3) copper(II)-catalyzed Eglinton coupling is the best strategy for obtaining diacetylene-modified alkane-1,ω-diols, because higher yields were obtained while avoiding the formation of by-products. Moreover, conversion of the diols into bipolar phospholipids was achieved by bis-phosphorylation with β-bromoethylphosphoric acid dichloride and subsequent quaternization with trimethylamine or dimethylamine. Finally, spectral data are presented for novel single-chain, diacetylene-modified bolaphospholipids with promising potential as starting molecules in the formation of polymerizable and, thus, thermostable nanofibers.