Synthesis of steroidal [4,6-b,c]-benzothiazepines, a new class of aromatase inhibitor

1995 ◽  
Vol 73 (12) ◽  
pp. 2185-2189 ◽  
Author(s):  
Herbert L. Holland ◽  
Sudalaiyandi Kumaresan ◽  
Gingipalli Lakshmaiah
Keyword(s):  
Aromatase Inhibitor ◽  
Michael Addition ◽  
Competitive Inhibitor ◽  
Crystallographic Analysis ◽  
X Ray ◽  
New Class ◽  
Acidic Conditions

Several steroidal [4,6-b,c]benzothiazepines have been prepared via base-catalyzed Michael addition of 2-aminothiophenol to 3β,17β-diacetoxyandrost-4-en-6-one. The product of this reaction has the 4β,5α stereochemistry, but cyclizes to a benzothiazepine with the steroidal 4β,5β configuration, confirmed by X-ray crystallographic analysis. 2-Aminothiophenol reacts with 3β,17β-diacetoxyandrost-4-en-6-one under acidic conditions to give a steroidal 6-spiro-benzothiazole. An androst-4-ene-3,17-dione-based [4,6]benzothiazepine has been shown to be a moderate competitive inhibitor of the human placental aromatase enzyme with IC50 = 42.3 µM. Keywords: steroid, aromatase, benzothiazepine.

scholarly journals Addition of some 6-amino-4-aryl-2(1H)-pyridones to phenylisocyanate and related reactions

2019 ◽  
Vol 74 (2) ◽  
pp. 191-195
Author(s):  
Lyubomir Dimitrov Raev ◽  
Ivo Christov Ivanov ◽  
Silviya Georgieva Agontseva
Keyword(s):  
Michael Addition ◽  
Acetyl Derivative ◽  
Phenyl Isocyanate ◽  
Crystallographic Analysis ◽  
Molar Ratio ◽  
X Ray ◽  
The Michael Addition

AbstractThe Michael addition of enaminoesters to coumarins leads to the formation of the rearranged adduct 1 whose structure has been previously elucidated by X-ray crystallographic analysis. Now, N- and/or O-carbamoylation of the 6-amino-2-pyridone 1 by treatment with phenyl isocyanate in a molar ratio of 1:1 and 1:2 gave N-mono- (2a) or N,O-bis-(phenylcarbamoyl) (3) derivatives, respectively. Further transformations of the corresponding new 2-pyridone derivative 2a into the O-acetyl derivative 2b and the chromeno[3,4-c]pyridine 4 are reported as well.

A Base-Promoted One-Pot Asymmetric Friedel–Crafts Alkylation/Michael Addition of 4-Substituted Indoles

Synthesis ◽  
2019 ◽  
Vol 52 (08) ◽  
pp. 1215-1222
Author(s):  
Robert Connon ◽  
Laura Carroll ◽  
Patrick J. Guiry
Keyword(s):  
Michael Addition ◽  
Crystallographic Analysis ◽  
Indole Derivatives ◽  
One Pot ◽  
X Ray ◽  
Excellent Yield ◽  
Tricyclic Core ◽  
Cyclobutane Derivative

Herein, we report a base-promoted Zn(II)–bis(oxazoline)-catalyzed one-pot Friedel–Crafts alkylation/Michael addition of 3-(indol-4-yl)acrylonitrile derivatives with trans-β-nitrostyrenes to yield the tricyclic core of the ergoline skeleton in up to 71% yield and 85% ee. During the purification of 3-(indol-4-yl)acrylonitrile, the key substrate for catalytic studies, a novel trans-cis-trans-cyclobutane derivative, thought to be formed via a [2+2] light-promoted cycloaddition, was identified by X-ray crystallographic analysis. Finally, a novel class of 4-substituted bis(indole)methane derivatives were serendipitously prepared in excellent yield by reacting 4-substituted indole derivatives with 4-nitrobenzaldehyde. One bis(indole)methane was characterized by X-ray crystallographic analysis.

The chemistry of Eremophila spp. XVIII. A new class of diterpenes from Eremophila viscida

1983 ◽  
Vol 36 (5) ◽  
pp. 993 ◽  
Author(s):  
EL Ghisalberti ◽  
CH Hocart ◽  
PR Jefferies ◽  
GM Proudfoot ◽  
BW Skelton ◽  
...  
Keyword(s):  
Spectroscopic Data ◽  
Crystallographic Analysis ◽  
X Ray ◽  
New Class

Two new diterpenes have been isolated from the resin of E. viscida Endl. Evidence for their structure was obtained from spectroscopic data and from X-ray crystallographic analysis which show them to be members of a new class of diterpenes containing a C 5 extended acorane skeleton.

Base mediated dimerization of 2-tetradecynoic acid

1983 ◽  
Vol 61 (11) ◽  
pp. 2449-2454 ◽  
Author(s):  
Suzanne R. Abrams ◽  
J. Wilson Quail ◽  
Louis T. J. Delbaere
Keyword(s):  
Sodium Salt ◽  
Michael Addition ◽  
Dimethyl Ester ◽  
Crystallographic Analysis ◽  
Strong Base ◽  
X Ray ◽  
Crude Product ◽  
Monomethyl Ester

Under the influence of the very strong base, the sodium salt of 1,2-diaminoethane in 1,2-diaminoethane, 2-tetradecynoic acid is converted to 3-tetradecynoic acid (35%) and a novel dimer 3. Compound 3 ((Z)-2-(1-dodecynyl)-3-undecyl-pent-2-en-1,5-dioic diacid) is isolated as the monomethyl ester 1 after treatment of the crude product with methanolic HCl. The structures of 1 and 3 are deduced from an X-ray crystallographic analysis of the dimethyl ester 2 obtained by reaction of 1 with diazomethane. The dimer 3 is thought to arise from Michael addition of the dianion 4 of 3-tetradecynoic acid with the sodium salt of 2-tetradecynoic acid.

Absolute Konfiguration von (+)-1,2,3,4,6,7,8,8a-Octahydro-6-isochinolon- 8a-carbonsäuremethylester und die Stereochemie einer Kupfer-katalysierten asymmetrischen Michael-Reaktion / Absolute Configuration of Methyl (+)-1,2,3,4,6,7,8,8a-Octahydro-6-isoquinolone-8a-carboxylate and Stereochemistry of a Copper-Catalyzed Asymmetric Michael Reaction

2004 ◽  
Vol 59 (4) ◽  
pp. 375-379 ◽  
Author(s):  
Jens Christoffers ◽  
Wolfgang Frey ◽  
Heiko Scharl ◽  
Angelika Baro
Keyword(s):  
Absolute Configuration ◽  
Michael Addition ◽  
Michael Reaction ◽  
Addition Product ◽  
Crystallographic Analysis ◽  
Subsequent Reaction ◽  
X Ray ◽  
Quaternary Stereocenter ◽  
Asymmetric Michael Reaction

AbstractEnantiopure Boc-protected piperidine derivative (+)-5c, with a quaternary stereocenter, was obtained by copper-catalyzed, L-valine diethylamide-mediated Michael reaction. For determination of the absolute configuration, 5c was derivatized by cyclization with pyrrolidine/AcOH to give compound 6 with bicyclo[4.4.0]-constitution, deprotection of the amino function with TFA and subsequent reaction with 2-iodobenzoic acid to yield the crystalline bicyclic amide 7. X-ray crystallographic analysis confirmed the constitution of compounds 5c and 6 and established the (R) configuration of 7. Thus, starting Michael addition product (+)-5c has to be (S) configured, because an epimerization at the quaternary stereocenter is excluded. This result is in accordance with our working model of the Cu-catalyzed, auxiliary-assisted Michael reaction.

Structure–sweetness relationships for fructose analogs. Part II. Synthesis and properties of 1,6-dihydroxy-2-hexanone, a simple analog of the ketohexoses, and X-ray structure determination of the corresponding dianhydrides

1985 ◽  
Vol 63 (6) ◽  
pp. 1222-1227 ◽  
Author(s):  
Walter A. Szarek ◽  
Olivier R. Martin ◽  
Robert J. Rafka ◽  
T. Stanley Cameron
Keyword(s):  
Structure Determination ◽  
Deuterium Oxide ◽  
Crystallographic Analysis ◽  
Open Chain ◽  
X Ray ◽  
Acidic Conditions ◽  
Simple Analog

Labile 1,6-dihydroxy-2-hexanone (4) was prepared from the corresponding triol by selective di-O-tritylation, Collins oxidation, and careful detritylation of the resulting keto compound 3 under mild, acidic conditions. As shown by its 1Hmr and 13Cmr spectra, 4 exists as a 3:2 mixture of open-chain and cyclic forms, respectively, at equilibrium in deuterium oxide (25 °C). Upon standing, 4 is slowly converted into a hemiacetalic dimer. Under acidic conditions, dehydrative dimerization takes place to give the corresponding tricyclic dianhydride, one or both of the possible isomers (1:1 mixture) of which being formed according to the presence or absence of water in the medium. The structure (trans) of the thermodynamic isomer 5 was firmly established by an X-ray crystallographic analysis.

scholarly journals Concise Diastereoselective Total Synthesis of (±)-Parvistemonine A

Synlett ◽  
2020 ◽  
Vol 31 (18) ◽  
pp. 1800-1804
Author(s):  
Kazuyuki Sugita ◽  
Rintaro Matsuo ◽  
Ayumu Miyashita ◽  
Motoi Kuwabara ◽  
Shinya Adachi ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Michael Addition ◽  
Wittig Reaction ◽  
Crystallographic Analysis ◽  
Mitsunobu Reaction ◽  
X Ray ◽  
Linear Sequence ◽  
Relative Stereochemistry ◽  
Key Steps ◽  
First Time

AbstractWe have developed a concise diastereoselective total synthesis of (±)-parvistemonine A. By using a Mukaiyama–Michael addition, an aza-Wittig reaction, a Paal–Knorr pyrrole synthesis, an acid-mediated annulation, and a Mitsunobu reaction as key steps, we achieved a total synthesis in which the longest linear sequence was ten steps and the overall yield was 19.6%. Additionally, the relative stereochemistry of parvistemonine A was confirmed by X-ray crystallographic analysis for the first time.

A One-Pot Intramolecular Tandem Michael–Aldol Annulation Reaction for the Synthesis of Chiral Pentacyclic Terpenes

Synthesis ◽  
2019 ◽  
Vol 51 (21) ◽  
pp. 3964-3972
Author(s):  
Jianyu Lu ◽  
Serkan Koldas ◽  
Huafang Fan ◽  
John Desper ◽  
Victor W. Day ◽  
...  
Keyword(s):  
Michael Addition ◽  
Aldol Condensation ◽  
Crystallographic Analysis ◽  
Side Chain ◽  
One Pot ◽  
X Ray ◽  
Double Ring ◽  
Stereogenic Centers

A chiral tricyclic terpene possessing a 6,6,6-tricyclic framework and a 3,3-dimethyl-7-oxooctylidenyl side chain undergoes a double ring-closing reaction to give two chiral pentacyclic terpenes in a ratio of 4:3 via an intramolecular Michael addition followed by aldol condensation under basic conditions. Three new stereogenic centers are introduced in the initial Michael annulation reaction. Stereoselective installation of an ethoxycarbonyl group at C17 of the two pentacyclic terpenes separately gives the corresponding highly functionalized pentacyclic terpenoids with seven stereogenic centers. The structures and stereochemistry of key intermediates and products are established through X-ray crystallographic analysis. A mechanism is proposed for explaining the stereochemistry in the Michael annulation reaction.

scholarly journals Synthesis of 2H-Chromene-4-Carbonitriles Via Trimethylsilyl Cyanide

2018 ◽  
Vol 42 (6) ◽  
pp. 297-299 ◽  
Author(s):  
Demin Ren ◽  
Hexiu Liu ◽  
Yulin Huang ◽  
Xinliang Fu ◽  
Xiaofang Li
Keyword(s):  
Michael Addition ◽  
Crystallographic Analysis ◽  
X Ray ◽  
Trimethylsilyl Cyanide ◽  
Tetrabutylammonium Fluoride ◽  
Elimination Pathway

A number of 2-aryl-2 H-chromene-4-carbonitriles were synthesised by cyanation of 2-aryl-3-nitro-2 H-chromenes using trimethylsilyl cyanide (TMSCN) in the presence of tetrabutylammonium fluoride (TBAF) in moderate yields via a Michael addition/elimination pathway. The structures of all the products were characterised thoroughly by NMR, IR and HRMS spectroscopy and X-ray crystallographic analysis.

scholarly journals Synthesis of 2-(1-Oxo-2,3-Dihydro-1H-Pyrrolizin-2-yl)-2-(Aryl)Acetonitrile Derivatives Via Michael Addition of Trimethylsilyl Cyanide

2018 ◽  
Vol 42 (9) ◽  
pp. 467-470 ◽  
Author(s):  
Demin Ren ◽  
Jiaying Lei ◽  
Xianyong Yu ◽  
Yulin Huang ◽  
Xiaofang Li
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Michael Addition ◽  
High Resolution Mass Spectrometry ◽  
Crystallographic Analysis ◽  
X Ray ◽  
Trimethylsilyl Cyanide ◽  
Tetrabutylammonium Fluoride ◽  
High Resolution Mass ◽  
Resolution Mass

Several 2-aryl-2-(1-oxo-2,3-dihydro-1 H-pyrrolizin-2-yl)acetonitrile derivatives were synthesised by Michael addition of ( E)-2-arylidene-2,3-dihydro-1 H-pyrrolizin-1-ones with trimethylsilyl cyanide in the presence of tetrabutylammonium fluoride in moderate yields. The structures of all of the products were fully characterised by NMR, IR and high-resolution mass spectrometry, together with X-ray crystallographic analysis.

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