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.

Protecting Groups

2008 ◽  
Author(s):  
Jie Jack Li ◽  
Chris Limberakis ◽  
Derek A. Pflum
Keyword(s):  
Low Temperature ◽  
Organic Synthesis ◽  
Secondary Alcohol ◽  
Primary Alcohol ◽  
Protecting Groups ◽  
Silyl Ether ◽  
Benzyl Ether ◽  
Protecting Group ◽  
Selective Protection ◽  
Death Taxes

In his book, Protecting Groups, Philip J. Kocieński stated that there are three things that cannot be avoided: death, taxes, and protecting groups. Indeed, protecting groups mask functionality that would otherwise be compromised or interfere with a given reaction, making them a necessity in organic synthesis. In this chapter, for each protecting group showcased, only the most widely used methods for protection and cleavage are shown. Also, this section is not comprehensive and only addresses some of the most common blocking groups in organic synthesis. For a thorough review of protecting groups, the reader should consult the following references: (a) Wuts, P. G. M.; Greene, T. W.; Protective Groups in Organic Synthesis, 4th ed.; Wiley: Hoboken, NJ, 2007; (b) Kocienski, P. J. Protecting Groups, 3rd edition.; Thieme: Stuggart, 2004. In this section, the formation and cleavage of eight protecting groups for alcohols and phenols are presented: acetate; acetonides for diols; benzyl ether; para-methoxybenzyl (PMB) ether; methyl ether; methoxymethylene (MOM) ether; tert-butyldiphenylsilyl (TBDPS) silyl ether; and tetrahydropyran (THP). Acetate is a convenient protecting group for alcohols—easy on and easy off. Selective protection of a primary alcohol in the presence of a secondary alcohol can be achieved at low temperature. The drawback of this protecting group is its incompatibility with hydrolysis and reductive conditions.

The Morken Synthesis of (+)-Discodermolide

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Clinical Trials ◽  
Primary Alcohol ◽  
Selective Reduction ◽  
Practical Approach ◽  
Silyl Ether ◽  
Protecting Group ◽  
Lead Structure ◽  
Anticancer Properties ◽  
Stereogenic Centers ◽  
Diastereoselective Addition

The anticancer properties of discodermolide 3 were exciting enough that Novartis undertook a commercial-scale total synthesis. While initial clinical trials were not suc­cessful, it is still a very promising lead structure. James P. Morken of Boston College developed (Angew. Chem. Int. Ed. 2014, 53, 9632) a practical approach, based on the Still–Gennari coupling of the phosphonate 1 with the aldehyde 2. The preparation both of 1 and of 2 showed to advantage the diene borylations that have been developed by the Morken group over the past several years. The alde­hyde 5 was prepared by enantioselective hydroformation of the protected acrolein 4. Borylation of pentadiene 6 followed by diastereoselective addition to 5 set, after oxi­dation, the three new stereogenic centers of 7. Ir-catalyzed hydroboration led to the primary alcohol, that was carried through aldehyde deprotection and oxidation to the ester 8. Oxidation of the alcohol to the acid 9 followed by activation with 10 and cou­pling with the anion 11 then completed the synthesis of 1. The preparation of the key Z-trisubstituted alkene chiron 16 again began with enantioselective hydroformylation of the allyl silyl ether 12 to 13. The addition of 14 proceeded with high diastereoselectivity. Nickel-catalyzed borylation of 15 was also highly diastereoselective, leading to an intermediate that was oxidized to the primary alcohol, then carried on the iodide 16. Pt-catalyzed enantioselective borylation of 6 followed by the addition of chloro­methyl lithium led, after oxidation, to the diol 17. Exposure of the derived bis tosyl­ate to potassium t-butoxide led to facile elimination of the homoallylic tosylate. The remaining tosyl protecting group was then removed reductively to give 18. The Roush reductive aldol protocol using the enolate derived from 19 was applied to the derived aldehyde, leading to 20, that was carried on to 21. Under carefully defined conditions, the E-enolate of 21 coupled efficiently with the allylic iodide 17 to give 2. Still–Gennari coupling with 1 to give 22 followed by selective reduction, deprotection, and lactonization then completed the synthesis of (+)-discodermolide 3.

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.

The Smith Synthesis of (−)-Calyciphylline N

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Secondary Alcohol ◽  
Primary Alcohol ◽  
Diels Alder ◽  
University Of Pennsylvania ◽  
Silyl Ether ◽  
Direct Oxidation ◽  
The Third ◽  
Secondary Center ◽  
Open Face ◽  
The University

The Daphniphyllum alkaloids are a diverse group, some of which exhibit potent bio­logical activity. Amos B. Smith III of the University of Pennsylvania envisioned (J. Am. Chem. Soc. 2014, 136, 870) the preparation of the bicyclo[2.2.2] core of (−)-calyciphylline N 3 by the intramolecular Diels–Alder cyclization of 1 to 2, with the silicon of 2 a surrogate for the secondary alcohol of 3. Following the precedent of Mori (Tetrahedron Asymm. 2005, 16, 685), the requi­site secondary center of 1 was set by methylation of the anion derived from the Evans acyl oxazolidinone 4. Reductive removal of the oxazolidinone led to the alcohol 5, that was reduced under Birch conditions, then isomerized with base to the desired conjugated diene 6. This was silylated with the alkenyl silane 7 to give the triene 1. Direct thermal cyclization of 1 gave a mixture of all four possible diastereomers of the cycloadduct. Fortunately, the Lewis acid-activated cyclization delivered 2 as the dominant diastereomer. To differentiate the two ends of the alkene, the ester of 2 was extended to the alco­hol 8. Epoxidation occurred from the more open face of the alkene, setting the stage for intramolecular opening and oxidation to give 9. Reduction with SmI2 and protec­tion then completed the preparation of the ketone 10. The third quaternary center of 3 was constructed by acetylation of 10 followed by Pd-catalyzed allylation, to give 11. On exposure to LDA, the derived iodide 12 smoothly cyclized to the cycloheptanone 13, the structure of which was confirmed by X-ray analysis. The alkene of 13 was converted to the primary alcohol, which was protected. The aryl lithium 14 then was used to selectively open the cyclic silyl ether, to give 15. Coupling with phthalimide followed by carbonylative vinylation of the derived vinyl triflate delivered the dienone 16. Exposure to HBF4 effected the desired Nazarov cyclization, and at the same time converted the aryl silane to the fluorosilane, set for the Tamao oxidation that revealed the secondary alcohol. The two alcohols were sequentially protected to give 17. Direct oxidation of the primary silyl ether gave the aldehyde.

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.

Enantioselective, Protecting-Group-Free Total Synthesis of Sarpagine Alkaloids-A Generalized Approach

2014 ◽  
Vol 54 (1) ◽  
pp. 315-317 ◽  
Author(s):  
Sebastian Krüger ◽  
Tanja Gaich
Keyword(s):  
Total Synthesis ◽  
Protecting Group

scholarly journals A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

2013 ◽  
Vol 9 ◽  
pp. 2028-2032 ◽  
Author(s):  
Martin Zahel ◽  
Peter Metz
Keyword(s):  
Total Synthesis ◽  
Enantioselective Synthesis ◽  
Englerin A ◽  
Epoxide Opening

(−)-Oxyphyllol was prepared in only 4 steps from an epoxy enone that already served as an intermediate for the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions.

Domino Primary Alcohol Oxidation-Wittig Reaction: Total Synthesis of ABT-418 and (E)-4-Oxonon-2-enoic Acid

Synthesis ◽  
2004 ◽  
Vol 2004 (11) ◽  
pp. 1859-1863 ◽  
Author(s):  
Santosh Tilve ◽  
Jyoti Shet ◽  
Vidya Desai
Keyword(s):  
Total Synthesis ◽  
Wittig Reaction ◽  
Primary Alcohol ◽  
Alcohol Oxidation ◽  
Enoic Acid

The Roush Synthesis of ( + )-Superstolide A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Malignant Cell ◽  
Alder Reaction ◽  
Diels Alder ◽  
Protecting Group ◽  
The Third ◽  
Diels Alder Reaction ◽  
Single Diastereomer ◽  
Superstolide A ◽  
One Step ◽  
Fourth Component

( + )-Superstolide A 3, isolated from the New Caledonian sponge Neosiphonia superstes, shows interesting cytotoxicity against malignant cell lines at ~ 4 ng/mL concentration. The key transformation in the synthesis of 3 described (J. Am. Chem. Soc. 2008, 130, 2722) by William R. Roush of Scripps Florida was the transannular Diels-Alder cyclization of 2, which established, in one step with high diastereocontrol, both the cis decalin and the macrolactone of 3. The octaene 1 was assembled from four stereodefined fragments. The first, the linchpin 6, was prepared from the stannyl aldehyde 4. Homologation gave the enyne 5, which on hydroboration and oxidation gave 6. Earlier, Professor Roush had optimized the crotylation of the protected alaninal 7. In this case, the Brown reagent 8 delivered the desired Felkin product 9. Protection followed by ozonolysis gave the aldehyde 10. Crotylation with the Roush-developed tartrate 11 then gave the alkene 12, setting the stage for conversion to the iodide 13. Coupling of 13 with 6 completed the preparation of 14. The third component of (+)-superstolide A 3, the phosphonium salt 21, was assembled by Brown allylation of the aldehyde 15, to give 17. Protecting group interchange followed by ozonolysis delivered 18, which via Still-Gennari homologation was carried on to 21. Condensation with the fourth component, the aldehyde 22 , and esterification with 14 then gave 1. Under high dilution Suzuki conditions 1 was converted to 2. Storage in CDCl3 for five days, or brief warming, cyclized 2 to a single diastereomer of the transannular Diels-Alder product, that was carried on to (+)-superstolide A 3. While acyclic trienes comparable to 2 could be induced to cyclize, the transannular Diels-Alder reaction proceeded with much higher diastereocontrol.

ChemInform Abstract: Expedient Synthesis of Large-Ring trans-Enamide Macrolides by CuI-Mediated Intramolecular Coupling of Vinyl Iodide with Amide: Total Synthesis of Palmyrolide A.

ChemInform ◽  
2016 ◽  
Vol 47 (37) ◽  
Author(s):  
Jhillu Singh Yadav ◽  
Borra Suresh ◽  
Pabbaraja Srihari
Keyword(s):  
Total Synthesis ◽  
Large Ring ◽  
Vinyl Iodide
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