62235-06-7Relevant academic research and scientific papers
Substrate Requirements for Lepidopteran Farnesol Dehydrogenase
Sen, Stephanie E.,Garvin, Gail M.
, p. 820 - 825 (1995)
Farnesol dehydrogenase of the lepidopteran Manduca sexta shows surprisingly high substrate specificity, as inferred from the binding of substrate analogs and (potential) alternative substrates.The enzyme is not a simple alcohol dehydrogenase, as ethanol and octanol are not substrates for this enzyme.The enzyme also does not appear to be related to Drosophila alcohol dehydrogenase since secondary alcohols are much poorer inhibitors.Several farnesol analogs with modified carbon skeletons have been tested for their ability to function as inhibitors of farnesoldehydrogenase.Substrate competition studies indicate that the enzyme is highly specific for alcohols with Δ-2,3 unsaturation, trans allylic olefin geometry, and alkyl chain hydrophobicity corresponding to at least three isoprene units.These results suggest that farnesol dehydrogenase is a unique dehydrogenase that should be further examined as a potential target for anti juvenoid development.Keywords: Farnesol dehydrogenase; juvenile hormone biosynthesis; Manduca sexta; substrate analogs
Highly Selective and Catalytic Generation of Acyclic Quaternary Carbon Stereocenters via Functionalization of 1,3-Dienes with CO2
Chen, Xiao-Wang,Zhu, Lei,Gui, Yong-Yuan,Jing, Ke,Jiang, Yuan-Xu,Bo, Zhi-Yu,Lan, Yu,Li, Jing,Yu, Da-Gang
, p. 18825 - 18835 (2019/11/28)
The catalytic asymmetric functionalization of readily available 1,3-dienes is highly important, but current examples are mostly limited to the construction of tertiary chiral centers. The asymmetric generation of acyclic products containing all-carbon quaternary stereocenters from substituted 1,3-dienes represents a more challenging, but highly desirable, synthetic process for which there are very few examples. Herein, we report the highly selective copper-catalyzed generation of chiral all-carbon acyclic quaternary stereocenters via functionalization of 1,3-dienes with CO2. A variety of readily available 1,1-disubstituted 1,3-dienes, as well as a 1,3,5-triene, undergo reductive hydroxymethylation with high chemo-, regio-, E/Z-, and enantioselectivities. The reported method features good functional group tolerance, is readily scaled up to at least 5 mmol of starting diene, and generates chiral products that are useful building blocks for further derivatization. Systemic mechanistic investigations using density functional theory calculations were performed and provided the first theoretical investigation for an asymmetric transformation involving CO2. These computational results indicate that the 1,2-hydrocupration of 1,3-diene proceeds with high π-facial selectivity to generate an (S)-allylcopper intermediate, which further induces the chirality of the quaternary carbon center in the final product. The 1,4-addition of an internal allylcopper complex, which differs from previous reports involving terminal allylmetallic intermediates, to CO2 kinetically determines the E/Z- and regioselectivity. The rapid reduction of a copper carboxylate intermediate to the corresponding silyl-ether in the presence of Me(MeO)2SiH provides the exergonic impetus and leads to chemoselective hydroxymethylation rather than carboxylation. These results provide new insights for guiding further development of asymmetric C-C bond formations with CO2
Herbivore-induced and floral homoterpene volatiles are biosynthesized by a single P450 enzyme (CYP82G1) in Arabidopsis
Lee, Sungbeom,Badieyan, Somayesadat,Bevan, David R.,Herde, Marco,Gatz, Christiane,Tholl, Dorothea
scheme or table, p. 21205 - 21210 (2011/10/04)
Terpene volatiles play important roles in plant-organism interactions as attractants of pollinators or as defense compounds against herbivores. Among the most common plant volatiles are homoterpenes, which are often emitted from night-scented flowers and from aerial tissues upon herbivore attack. Homoterpene volatiles released from herbivore-damaged tissue are thought to contribute to indirect plant defense by attracting natural enemies of pests. Moreover, homoterpenes have been demonstrated to induce defensive responses in plant-plant interaction. Although early steps in the biosynthesis of homoterpenes have been elucidated, the identity of the enzyme responsible for the direct formation of these volatiles has remained unknown. Here, we demonstrate that CYP82G1 (At3g25180), a cytochrome P450 monooxygenase of the Arabidopsis CYP82 family, is responsible for the breakdown of the C20-precursor (E,E)-geranyllinalool to the insect-induced C16-homoterpene (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT). Recombinant CYP82G1 shows narrow substrate specificity for (E,E)- geranyllinalool and its C 15-analog (E)-nerolidol, which is converted to the respective C 11-homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT). Homology-based modeling and substrate docking support an oxidative bond cleavage of the alcohol substrate via syn-elimination of the polar head, together with an allylic C-5 hydrogen atom. CYP82G1 is constitutively expressed in Arabidopsis stems and inflorescences and shows highly coordinated herbivoreinduced expression with geranyllinalool synthase in leaves depending on the F-box protein COI-1. CYP82G1 represents a unique characterized enzyme in the plant CYP82 family with a function as a DMNT/TMTT homoterpene synthase.
Enantio- and diastereoselective stepwise cyclization of polyprenoids induced by chiral and achiral LBAs. A new entry to (-)-ambrox, (+)-podocarpa-8,11,13-triene diterpenoids, and (-)-tetracyclic polyprenoid of sedimentary origin
Ishihara, Kazuaki,Ishibashi, Hideaki,Yamamoto, Hisashi
, p. 3647 - 3655 (2007/10/03)
An enantio- and diastereoselective stepwise cyclization of polyprenoids induced by Lewis acid-assisted chiral Bronsted acids (chiral LBAs) and achiral LBAs is described. In particular, the absolute stereocontrol in the initial cyclization of polyprenoids to form an A-ring induced by chiral LBAs and the importance of the nucleophilicity of the internal terminator in polyprenoids for the relative stereocontrol in subsequent cyclization are demonstrated. (-)-Ambrox was synthesized via the enantioselective cyclization of (E,E)-homofarnesyl triethyrsily ether with triethylsilyl ether with tin(IV) chloride-coordinated (R)-2-(o-fluorobenzyloxy)-2′-hydroxy-1,1′-binaphthyl ((R)-BINOL-o-FBn) and subsequent diastereoselective cyclization with CF3CO2H·SnCl4 as key steps. Protection of (E,E)-homofarnesol by a triethylsilyl group increased the enantioselectivity of chiral LBA-induced cyclization and both the chemical yield and diastereoselectivity in the subsequent cyclization. The enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group was also induced by (R)-BINOL-o-FBn·SnCl4. Several optically active podocarpa-8,11,13-triene diterpenoids and (-)-tetracyclic polyprenoid of sedimentary origin were synthesized (75-80% ee) by the enantioselective cyclization of homo(polyprenyl)benzene derivatives induced by (R)-BINOL-o-FBn·SnCl4 and subsequent diastereoselective cyclization induced by BF3-Et2O/EtNO2 or CF3CO2H·SnCl4.
Olefination and hydroxymethylation of aldehydes using Knochel's (dialkoxyboryl)methylcopper reagents
Sakai, Masaaki,Saito, Syunn,Kanai, Gen,Suzuki, Akira,Miyaura, Norio
, p. 915 - 924 (2007/10/03)
The in-situ preparation of [(Me2C)2O2BCH2]Cu(CN)ZnI (3) from Knochel's (dialkoxyboryl)-methylzinc reagent (2) and CuCN·2LiCl in THF, followed by its addition to aldehyde in the presence of boron trifluoride etherate yielded rather stable β-hydroxyalkylboronates (5). The thermal dehydroxyboronation or the alkaline hydrogen peroxide oxidation of 5 gave the corresponding alkenes (6) or 1,2-alkanediols (7) in high yields. The reaction provides a simple procedure for the olefination or the hydroxymethylation of aldehydes.
Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. II. Structure elucidation and total synthesis
Kogen, Hiroshi,Tago, Keiko,Kaneko, Satoru,Hamano, Kiyoshi,Onodera, Kaori,Haruyama, Hideyuki,Minagawa, Katsuhiro,Kinoshita, Takeshi,Ishikawa, Tomio,Tanimoto, Tatsuo,Tsujita, Yoshio
, p. 624 - 630 (2007/10/03)
Schizostatin (1) has been isolated as a potent and selective inhibitor of squalene synthase. Its structure has been determined using spectroscopic methods: the compound is shown to be a diterpenoid which has a trans-dicarboxylic acid moiety. Total synthesis of schizostatin (1) was achieved by the highly regio- and stereoselective coupling reaction of an allylic bromide with a barium reagent. The Z-isomer 16 was also prepared using the stereoselective syn-addition of an organocopper reagent to acetylenedicarboxylate.
α-phosphonocarboxylate squalene synthetase inhibitors
-
, (2008/06/13)
α- Phosphonocarboxylate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula STR1 wherein R1 is a lipophilic group which contains at least 7 carbons and is substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl or optionally substituted aryl; Z is H, halogen, hydroxy, hydroxyalkyl or lower alkyl; R2 and R3 are independently H, metal ion or other pharmaceutically acceptable cation, or a prodrug ester; R4 is H, metal ion or other pharmaceutically acceptable cation, lower alkyl, lower alkenyl, arylalkyl, aryl or a prodrug ester.
Phosphorus-containing squalene synthetase inhibitors
-
, (2008/06/13)
Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure STR1 wherein m is 0, 1, 2 or 3; n is 0, 1, 2, 3 or 4; Y1 and Y2 are H or halogen; R2, R3 and R4 may be the same or different and are independently H, metal ion, C1 to C8 alkyl or C3 to C12 alkenyl; X is O, S, NH or NCH2 R15 wherein R15 is H or C1 to C5 alkyl; and R1 is R5 --Q1 --Q2 --Q3 -- wherein R5, Q1, Q2 and Q3 are as defined herein; and when m is o, X is other than S; and if m is o and X is 0, then n is 1, 2, 3 or 4; including all stereoisomers thereof.
Bisphosphonate squalene synthetase inhibitors and method
-
, (2008/06/13)
Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure STR1 and analogs thereof, wherein R1, R2, R3 and R4 are the same or different and are H, lower alkyl, a metal ion or a prodrug ester; R5 is H, halogen or lower alkyl; Zq is substituted alkenyl, substituted alkynyl, mixed alkenyl-alkynyl or substituted phenylalkyl or, phenylalkenyl or phenylalkynyl, or alkyl, including all stereoisomers thereof. New methods for using such compounds to inhibit cholesterol biosynthesis are also provided.
Synthesis of Inhibitors of 2,3-Oxidosqualene-lanosterol Cyclase: Conjugate Addition of Organocuprates to N-(Carbobenzyloxy)-3-carbomethoxy-5,6-dihydro-4-pyridone
Dodd, Dharmpal S.,Oehlschlager, Allan C.
, p. 2794 - 2803 (2007/10/02)
Synthesis of ammonium ion analogues of the first cationic intermediate, 5, presumed to be formed during the cyclization of 2,3-oxidosqualene by 2,3-oxidosqualene-lanosterol cyclase are reported.The required 2,3-substituted-4-piperidinols are prepared by c
