117570-31-7Relevant articles and documents
Enantioselective synthesis of multisubstituted biaryl skeleton by chiral phosphoric acid catalyzed desymmetrization/kinetic resolution sequence
Mori, Keiji,Ichikawa, Yuki,Kobayashi, Manato,Shibata, Yukihiro,Yamanaka, Masahiro,Akiyama, Takahiko
supporting information, p. 3964 - 3970 (2013/04/24)
Described herein is the enantioselective synthesis of multisubstituted biaryl derivatives by chiral phosphoric acid catalyzed asymmetric bromination. Two asymmetric reactions (desymmetrization and kinetic resolution) proceeded successively to afford chiral biaryls in excellent enantioselectivities (up to 99% ee). Both experimental and computational studies suggested that this excellent selectivity could be achieved via a highly organized hydrogen bond network among a substrate, a catalyst (chiral phosphoric acid), and a brominating reagent (N-bromophthalimide).
Combined directed remote metalation-transition metal catalyzed cross coupling strategies: The total synthesis of the aglycones of the gilvocarcins V, M, and E and arnottin I
James, Clint A.,Snieckus, Victor
supporting information; experimental part, p. 4080 - 4093 (2009/09/30)
(Chemical Equation Presented) A key directed remote metalation (DreM)-carbamoyl migration strategy was applied in an efficient synthesis of the naturally occurring 6H-naphtho[1,2-b]benzopyran-6-one defucogilvocarcin V (1a, Scheme 11). The required biarylcarbamate 33d was best prepared by a high yielding Suzuki coupling reaction of 31a with the differentially protected trioxygenated naphthalene coupling partner 32d which was synthesized using a selective acylation of a juglone derivative. In the late stages of the synthesis, the triflate 39 served as the common intermediate to install the required C-8 vinyl group of 1a (Stille coupling) as well as the required substituents for the preparation of defucogilvocarcins M (1b) and E (1c). A variety of protecting group strategies were investigated and provided insight into which groups are preferred for the DreM-carbamoyl migration process. The strategic lessons learned from this total synthesis were applied in the successful total synthesis of the structurally similar natural product arnottin I (2).
A highly efficient strategy for the synthesis of 3-substituted salicylic acids by either directed ortho-lithiation or halogen-metal exchange of substituted mom protected phenols followed by carboxylation
Lau, Stephen Y.W.,Keay, Brian A.
, p. 1541 - 1545 (2007/10/03)
A highly efficient synthesis of various 3-substituted salicylic acids is described starting from inexpensive starting materials and requiring no special apparatus.
Fluorophenols and (trifluoromethyl)phenols as substrates of site-selective metalation reactions: To protect or not to protect
Marzi, Elena,Mongin, Florence,Spitaleri, Andrea,Schlosser, Manfred
, p. 2911 - 2915 (2007/10/03)
O-Methoxymethyl (MOM) protected fluorophenols can be cleanly metalated and subsequently be submitted to site-selective electrophilic substitution. The 2- and 4-isomers exhibit ambivalent reactivity: deprotonation occurs at the position adjacent to the oxygen when butyllithium is employed whereas the position adjacent to the fluorine is attacked by the superbasic mixture of butyllithium and potassium tert-butoxide (LIC-KOR). The MOM-protected (trifluoromethyl)-phenols react exclusively at oxygen-neighboring positions. The meta isomer provides another example of optional site selectivity, undergoing hydrogen/metal exchange at the 2-position with the LIC-KOR reagent and at the 6-position with sec-butyllithium. Unprotected (trifluoromethyl)phenols can also be ortho-metalated after O-deprotonation, although the products are formed in only moderate yields.
Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators
Kalgutkar, Amit S.,Kozak, Kevin R.,Crews, Brenda C.,Hochgesang Jr., G. Phillip,Marnett, Lawrence J.
, p. 4800 - 4818 (2007/10/03)
All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
AMALOGUES MORPHINIQUES DERIVES DES TETRA- ET HEXAHYDRODIBENZOFURANES I - SYNTHESE ET EPOXYDATION STEREOSPECIQUES DES ARYLALKYLCYCLOHEXENES INTERMEDIAIRES
Labidalle, Serge,Min, Zhang Yong,Reynet, Annick,Moskowitz, Henri,Vierfond, Jean-Michel,et al.
, p. 1159 - 1170 (2007/10/02)
Par transposition de Claisen-Eachenmoser, on a fixe sur une serie d'aryl-1 cyclohexena-1 ols-2 une chaine dimethylacetamidee.Une epoxydation stereospecifique des composes obtenus conduit a des composes bicyclique intermediares dans la synthese d'analogues morphiniques.
