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.

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.

Catalyst-Free One-Pot Synthesis of Novel Heteroarylamine Substituted Furo[3,2-c]coumarins

Synlett ◽  
2018 ◽  
Vol 29 (12) ◽  
pp. 1589-1592 ◽  
Author(s):  
Abolfazl Olyaei ◽  
Mahnaz Saraei ◽  
Reyhaneh Khoeiniha
Keyword(s):  
Michael Addition ◽  
Aldol Condensation ◽  
Ring Closure ◽  
Dehydration Reaction ◽  
One Pot ◽  
Catalyst Free ◽  
One Pot Synthesis ◽  
Tandem Process ◽  
First Time

A high-yielding cyclocondensation of 4-hydroxycoumarin, phenylglyoxal monohydrate, and heteroarylamines proceeds without catalysis, which gives novel functionalized furo[3,2-c]coumarins and heteroarylamino alkylation of coumarin products in acetonitrile under reflux, is reported for the first time. This tandem process involves sequentially an aldol condensation, Michael addition, a ring closure, and dehydration reaction.

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.

Stereocontrolled construction of six vicinal stereogenic centers on a hexahydroxanthone framework through a formal [2+1+3] annulation

2019 ◽  
Vol 55 (93) ◽  
pp. 14003-14006 ◽  
Author(s):  
Shun-Qin Chang ◽  
Xiong Zou ◽  
Yi Gong ◽  
Xue-Wen He ◽  
Xiong-Li Liu ◽  
...  
Keyword(s):  
Michael Addition ◽  
One Pot ◽  
Stereogenic Centers

The first example of a bifunctional donor–donor 3C synthon formed in situ from an activated methine with nitromethane through a [2+1] Michael addition, further directing a one-pot organocascade Michael/Henry cycloaddition was developed.

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.

scholarly journals Synthesis, Characterization and HPLC Analysis of the (1S,2S,5R)-Diastereomer and the Enantiomer of the Clinical Candidate AR-15512

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 906
Author(s):  
Sergio Rodríguez-Arévalo ◽  
Eugènia Pujol ◽  
Sònia Abás ◽  
Carles Galdeano ◽  
Carmen Escolano ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Receptor Agonist ◽  
Hplc Analysis ◽  
Bioactive Compound ◽  
Crystallographic Analysis ◽  
X Ray ◽  
Cryo Electron Microscopy ◽  
Stereogenic Centers ◽  
Initial Starting ◽  
Clinical Candidate

AR-15512 (formerly known as AVX-012 and WS-12) is a TRPM8 receptor agonist currently in phase 2b clinical trials for the treatment of dry eye. This bioactive compound with menthol-like cooling activity has three stereogenic centers, and its final structure and absolute configuration, (1R,2S,5R), have been previously solved by cryo-electron microscopy. The route of synthesis of AR-15512 has also been reported, revealing that epimerization processes at the C-1 can occur at specific stages of the synthesis. In order to confirm that the desired configuration of AR-15512 does not change throughout the process and to discard the presence of the enantiomer in the final product due to possible contamination of the initial starting material, both the enantiomer of AR-15512 and the diastereomer at the C-1 were synthesized and fully characterized. In addition, the absolute configuration of the (1S,2S,5R)-diastereomer was determined by X-ray crystallographic analysis, and new HPLC methods were designed and developed for the identification of the two stereoisomers and their comparison with the clinical candidate AR-15512.

Studies towards the Total Synthesis of Kadcotrione B

Synthesis ◽  
2019 ◽  
Vol 52 (05) ◽  
pp. 735-743
Author(s):  
Julakanti Satyanarayana Reddy ◽  
Marri Gangababu ◽  
Patel Manimala ◽  
Aluru Rammohan ◽  
Jillu Singh Yadav
Keyword(s):  
Total Synthesis ◽  
Michael Addition ◽  
Aldol Condensation ◽  
Aldol Reaction ◽  
Side Chain ◽  
Wacker Oxidation ◽  
Efficient Approach ◽  
Salient Features ◽  
Robinson Annulation

A convergent and efficient approach towards the total synthesis of Kadcotrione B is described. For this purpose, the syntheses of two fragments, 6/6/5-fused tricyclic ring and C-9 side chain, were accomplished. The salient features of these syntheses are the utilization of aldol condensation, Evans aldol reaction, Horner–Wadsworth–Emmons olefination, Michael addition, Robinson annulation, and Wacker oxidation.

Remarkable Diastereoselectivity of the Thia-Michael Reaction on α,α′-Di[(E)-benzylidene]alkanones: Exclusive Formation of a meso Product

Synlett ◽  
2018 ◽  
Vol 29 (09) ◽  
pp. 1161-1166 ◽  
Author(s):  
Chayan Guha ◽  
Nayim Sepay ◽  
Tapas Halder ◽  
Asok Mallik
Keyword(s):  
Michael Addition ◽  
Michael Reaction ◽  
One Pot ◽  
X Ray ◽  
Amberlyst 15

Thia-Michael addition of thiophenol to α,α′-di[(E)-benzyl­idene]alkanones of both cyclic (six-membered) and acyclic varieties using anhydrous K2CO3 or amberlyst-15 as catalyst has been found to be highly diastereoselective at 15 °C. A one-pot protocol was developed for such reactions by a tandem aldol-thia-Michael process. The stereochemistry of the products was confirmed by X-ray crystallographic studies and in all cases formation of a meso product was observed.

Revised Absolute Configurations of Latifolic Acid and the Pyrrolizidine Alkaloid Latifoline

1988 ◽  
Vol 41 (11) ◽  
pp. 1781 ◽  
Author(s):  
JN Roitman ◽  
RY Wong
Keyword(s):  
Carboxylic Acid ◽  
Single Crystal ◽  
Pyrrolizidine Alkaloid ◽  
Crystallographic Analysis ◽  
Side Chain ◽  
X Ray ◽  
The Absolute ◽  
Absolute Stereochemistry

The absolute stereochemistry of (+)- latifolk acid has been determined by single-crystal X-ray crystallographic analysis to be (2S,3R,4R)-3- hydroxy-2,4-dimethyl-5-oxotetrahydrofuran-3-carboxylic acid. The configuration of the three chiral centres is opposite to that presently recorded in the literature. Accordingly, the configuration of the pyrrolizidine alkaloid, latifoline, which includes a latifolic acid side chain, must be revised.

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