A versatile method for the synthesis of γ-pyrones

2012 ◽  
Vol 90 (11) ◽  
pp. 954-964 ◽  
Author(s):  
Garrison E. Beye ◽  
Athanasios Karagiannis ◽  
Alieh Kazemeini ◽  
Dale E. Ward
Keyword(s):  
Total Synthesis ◽  
Ambient Temperature ◽  
Aldol Reaction ◽  
Trifluoromethanesulfonic Acid ◽  
Protecting Group ◽  
Triflic Acid ◽  
Step Procedure

A versatile three-step procedure to annulate a γ-pyrone onto a methylene ketone was developed involving (i) aldol reaction with a dithiolane-protected β-ketoaldehyde, (ii) oxidation of the aldol adduct to a β-diketone, and (iii) treatment of the resulting dithiolane-protected 1,3,5-trione with 2-iodoxybenzoic acid (IBX) and trifluoromethanesulfonic acid (triflic acid; TfOH) in acetonitrile at ambient temperature to give the corresponding γ-pyrone. Cyclization proceeded with IBX alone, but significantly improved yields were obtained with added acid, particularly triflic acid. A dithiolane was more effective than a dithiane or acyclic dithioacetal protecting group. The method was amenable to the preparation of a variety of substituted γ-pyrones simply by altering the initial aldol reactants. Overall yields of 50%–60% were obtained in six examples. The method was applied to prepare a key fragment for the total synthesis of baconipyrones A and C and siphonarin B.

Total Synthesis of the Pentacyclic Diterpenoid Tropone Hainanolidol

2000 ◽  
Vol 53 (10) ◽  
pp. 819 ◽  
Author(s):  
Barbara Frey ◽  
Adam P. Wells ◽  
Frances Roden ◽  
Ty Duong Au ◽  
David C. Hockless ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Oxidation Process ◽  
Aldol Reaction ◽  
Ring System ◽  
Protecting Group ◽  
X Ray ◽  
Catalysed Reaction ◽  
Process Methodology ◽  
The Stability ◽  
Carbonyl Function

The total synthesis of the unusual diterpenoid tropone, hainanolidol (1), discovered in the bark of the yew species, Cephalotaxus hainanensis, has been completed in 26 steps from 3,5-dimethylanisole. The intramolecular cyclopropanation reaction of the aryl ring in (30) by means of the rhodium mandelate-catalysed reaction of the diazoacetyl function was used to assemble the 5/7 ring system of (31), at the same time elaborating a cycloheptatriene moiety that could be transformed subsequently to the tropone functionality in the target molecule. While removing the acetal protecting group from (31) an unexpected Mukaiyama–type aldol process was induced by ZnBr2, affording (32), the structure of which was determined by X-ray analysis. With greater care, the aldehyde (33) could be obtained and the desired carbocyclic ring system completed by means of a base-catalysed aldol reaction with the newly formed hydroxyl being employed subsequently in the formation of the σ-lactone function in (35). Desilylation, reduction of the C-10 carbonyl function and brief exposure to acid finally afforded (1). This last step took advantage of the stability of the tropylium ion (40) to provide a ‘thermodynamic sink’ for the reaction outcome. The synthesis of (1) also constitutes a formal synthesis of the troponoid ether, harringtonolide (2), since this compound had been obtained previously from (1) by means of a transannular oxidation process. Methodology for the assembly of the tropone moiety in (1) and (2) was modelled on the simpler bi- and tricyclic systems, (13) and (22), respectively.

scholarly journals Application of sequential proline-catalyzed α-chlorination and aldol reactions in the total synthesis of 1-deoxygalactonojirimycin

2018 ◽  
Vol 96 (2) ◽  
pp. 144-147 ◽  
Author(s):  
Michael Meanwell ◽  
Mathew Sutherland ◽  
Robert Britton
Keyword(s):  
Total Synthesis ◽  
Aldol Reaction ◽  
Single Step ◽  
Carbon Skeleton ◽  
Aldol Reactions ◽  
Protecting Group ◽  
One Pot ◽  
Enantioselective Total Synthesis ◽  
Epoxide Opening ◽  
Structural Analogues

A short enantioselective total synthesis of 1-deoxygalactonojirimycin (migalastat) has been achieved that does not rely on chiral pool starting materials or biocatalysis. Instead, this synthesis exploits a one-pot proline-catalyzed α-chlorination and aldol reaction of a commercially available aldehyde to assemble the entire carbon skeleton in a single step. The key role played by a nitrogen protecting group in the final epoxide opening reaction is highlighted as is the amenability to access structural analogues using this route.

scholarly journals First Stereoselective Total Synthesis of Tumonoic Acid A and its Derivatives

SynOpen ◽  
2018 ◽  
Vol 02 (03) ◽  
pp. 0251-0255 ◽  
Author(s):  
G. Nagalatha ◽  
Siva Narala ◽  
A. Narsaiah
Keyword(s):  
Total Synthesis ◽  
Acid Derivative ◽  
Inhibitory Activity ◽  
Magnesium Chloride ◽  
Aldol Reaction ◽  
Calcium Oscillations ◽  
Inflammatory Activity ◽  
Protecting Group ◽  
Available N ◽  
Neocortical Neurons

An efficient protecting-group-free synthesis of tumonoic acid A and its derivatives has been accomplished. The synthesis started from commercially available n-octanal and employs the magnesium chloride catalysed anti-aldol reaction under the Evans protocol as the key step. Ethyl tumonoate A is a new tumonoic acid derivative with anti-inflammatory activity and inhibitory activity towards calcium oscillations in neocortical neurons.

Short Protecting Group-free Syntheses of CDE Synthon of Racemic Camptothecin

2020 ◽  
Vol 17 (7) ◽  
pp. 588-591
Author(s):  
Pingxuan Shao ◽  
Wei Lu ◽  
Lei Wang
Keyword(s):  
Total Synthesis ◽  
Future Development ◽  
Protecting Group ◽  
Short Route ◽  
The Future ◽  
Tricyclic Ketone

A practical and concise total synthesis of tricyclic ketone 7 (CDE ring), a valuable intermediate for the synthesis of racemic camptothecin and analogs, was described (8 chemical steps and 29% overall yield). The synthesis starts with two inexpensive, readily available materials and is operationally simple to perform. It is worth mentioning that the reported protecting group-free synthesis, with advantages of a short route, would be helpful for the future development of industry-scale syntheses of camptothecin-family alkaloids.

Short protecting-group-free synthesis of 5-acetylsulfanyl-histidines in water: novel precursors of 5-sulfanyl-histidine and its analogues

2016 ◽  
Vol 14 (44) ◽  
pp. 10473-10480 ◽  
Author(s):  
Sylvain Daunay ◽  
Remi Lebel ◽  
Laurence Farescour ◽  
Jean-Claude Yadan ◽  
Irene Erdelmeier
Keyword(s):  
Amino Acids ◽  
Protecting Group ◽  
One Pot ◽  
Step Procedure ◽  
Sulfur Containing

Natural and novel sulfur-containing amino acids are preparedviaa new regioselective one-pot two-step procedure.

Synthetic Approaches Towards the Total synthesis of tubulysin and its fragments: A review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nosheen Iqbal ◽  
Ameer Fawad Zahoor ◽  
Nasir Rasool ◽  
Samreen Gul Khan ◽  
Rabia Akhtar ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Claisen Rearrangement ◽  
Antitumor Agents ◽  
Aldol Reaction ◽  
Multidrug Resistant ◽  
Novel Drugs ◽  
Mukaiyama Aldol ◽  
Ic50 Values ◽  
Barbier Reaction ◽  
Synthetic Approaches

Background: Tubulysins, linear tetrapeptides show extraordinary cytotoxicity against various cancer cells, with IC50 values in nano or picomolar range. Due to their extremely vigorous anti-proliferative and antiangiogenic characteristics, tubulysins exhibit captivating prospects in the development of anticancer drugs. This review focuses on diverse routes for the total synthesis of natural and synthetic tubulysins as well as their fragments. Objective: The purpose of this review is to present the synthetic strategies for the development of antitumor agents, tubulysins. Conclusion: A range of synthetic pathways adopted for the total synthesis of tubulysins and their fragments have been described in this review. Synthesis of fragments, Tuv, Tup, and Tut can be accomplished by adopting appropriate strategies such as Manganese-mediated synthesis, Ireland-Claisen rearrangement, Mukaiyama aldol reaction, and Mannich process etc. Tubulysin B, D, U, V, and N14-desacetoxytubulysin H have been prepared through Mitsunobu reaction, tert-butanesulfinamide method, Tandem reaction, aza-Barbier reaction, Evans aldol reaction, and C-H activation strategies etc. The remarkable anticancer potential of tubulysins toward a substantiate target make them prominent leads for developing novel drugs against multidrug-resistant cancers.

Asymmetric Total Synthesis of (+)-Coprophilin

Synthesis ◽  
2017 ◽  
Vol 50 (06) ◽  
pp. 1301-1306 ◽  
Author(s):  
Isamu Shiina ◽  
Yuma Umezaki ◽  
Takatsugu Murata ◽  
Kyohei Suzuki ◽  
Takayuki Tonoi
Keyword(s):  
Total Synthesis ◽  
Aldol Reaction ◽  
Alder Reaction ◽  
Diels Alder ◽  
Core Structure ◽  
Asymmetric Total Synthesis ◽  
Diels Alder Reaction ◽  
Anticoccidial Agent

In this paper, we report the first total synthesis of (+)-coprophilin, an anticoccidial agent, by constructing the chiral linear precursor via a Mukaiyama–Evans aldol reaction and a stereoselective intramolecular Diels–Alder reaction. The proposed method can be used to provide large amounts of (+)-coprophilin, which exhibits a 3,4,5,6,7-pentasubstituted Δ1,2-octalin core structure.

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