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.

Total synthesis of (±)-9-deoxygoniopypyrone. Application of the iodocyclofunctionalization reaction of bold α-allenic alcohol derivatives

1998 ◽  
Vol 76 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Richard W Friesen ◽  
Suzanne Bissada
Keyword(s):  
Total Synthesis ◽  
Primary Alcohol ◽  
Silyl Ether ◽  
Protecting Group ◽  
Acetylenic Ester ◽  
The Third ◽  
Vicinal Diol ◽  
Epoxide Opening ◽  
Vinyl Iodide ◽  
Acidic Conditions

The synthesis of ( ±)-9-deoxygoniopypyrone (1) from the α-allenic alcohol 5 is described. Iodocyclofunctionaliztion of the N-tosyl carbamate derivative of 5 using I2 and Ag2CO3 provided, in a highly diastereoselective and regioselective fashion, the vinyl iodo syn-vicinal diol 4. Two routes were explored in order to introduce the third stereogenic centre in the molecule. Reductive deiodination of the vinyl iodide and diastereoselective epoxidation of the derived acetonide14 using mCPBA provided a mixture of epoxides 15 and 16 (2:1) in which the desired threo diastereomer predominated. Alternatively, dihydroxylation of acetonide 14 (OsO4, NMO) yielded a mixture of diols 21 and 22 (2:3) which were separated after monosilylation (TBDMSCl) of the primary alcohol. The major silyl ether erythro diastereomer 24 was converted to the desired epoxide 15 by mesylation (MsCl, Et3N) and epoxide formation (TBAF) with inversion of stereochemistry. The minor threo diastereomer 23 was also converted to the desired epoxide 15 (TBAF; ArSO2Cl; NaOMe). Epoxide opening was effected with lithium acetylide and the resulting alkyne 27 was carbonylated (MeLi, ClCO2Me) to afford the α , β-acetylenic ester 28. Semi hydrogenation over Lindlar's catalyst followed by protecting- group removal under acidic conditions provided ( ±)-8-epigoniodiol 30. Finally, conversion of 30 to ( ±)-9-deoxygoniopypyrone 1 was effected under basic conditions (DBU).Key words: ( ±)-9-deoxygoniopypyrone, α-allenic alcohol, iodocyclofunctionalization, syn-diol.

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 Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

2020 ◽  
Vol 16 ◽  
pp. 135-139
Author(s):  
Thomas J Cogswell ◽  
Craig S Donald ◽  
Rodolfo Marquez
Keyword(s):  
Total Synthesis ◽  
Protecting Group ◽  
Ring Closing Metathesis ◽  
One Pot ◽  
High Yields

A fast, protecting-group-free synthesis of dihydropyridinones has been developed. Starting from commercially available aldehydes, a novel one-pot amidoallylation gave access to diene compounds in good yields. Ring-closing metathesis conditions were then employed to produce the target dihydropyridinones efficiently and in high yields.

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