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Total Synthesis of (-)-Stemoamide
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
2007 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 72, no 11, 4246-4249 p.Article in journal (Refereed) Published
Abstract [en]

A stereocontrolled total synthesis of (-)-stemoamide (1) is presented. The synthesis starts from commercially available (S)-pyroglutaminol (4). A chemoselective iodoboration of 5 was used to access key intermediate 3. The beta,gamma-unsaturated azepine derivative 2 was obtained via a Pd(0)-catalyzed sp(2)-sp(3) Negishi cross-coupling using a Reformatsky nucleophile followed by a ring-closing metathesis reaction. The required C8-C9 trans-stereochemistry of 1 was accessed through a stereoselective bromolactonization/1,4-reduction sequence.

Place, publisher, year, edition, pages
2007. Vol. 72, no 11, 4246-4249 p.
Keyword [en]
Chemoselective iodoboration; Metathesis reaction; Reduction sequences; Alcohols; Derivatives; Reduction; Synthesis (chemical); Amides; alkaloid derivative; azepine derivative; glutamine derivative; palladium; pyroglutaminol; stemoamide; unclassified drug; article; catalysis; cross coupling reaction; drug structure; drug synthesis; reduction; Reformatsky reaction; ring closing metathesis; stereochemistry; Alkaloids; Azepines; Catalysis; Heterocyclic Compounds, 3-Ring; Lactones; Models, Molecular; Molecular Conformation; Molecular Structure; Stereoisomerism
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-7407DOI: 10.1021/jo070498oISI: 000246570200034PubMedID: 17451274Scopus ID: 2-s2.0-34249812712OAI: oai:DiVA.org:kth-7407DiVA: diva2:12425
Note
QC 20100820Available from: 2007-08-23 Created: 2007-08-23 Last updated: 2010-08-20Bibliographically approved
In thesis
1. Stereoselective Synthesis of Amino Alcohols: Applications to Natural Product Synthesis
Open this publication in new window or tab >>Stereoselective Synthesis of Amino Alcohols: Applications to Natural Product Synthesis
2007 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

This thesis is divided into four separate parts with amino alcohols as the common feature.

The first part of the thesis describes the development of an efficient three-component approach to the synthesis of α-hydroxy-β-amino esters. Utilizing a highly diastereoselective Rh(II)-catalyzed 1,3-dipolar cycloaddition of carbonyl ylides to various aldimines, syn-α-hydroxy-β-amino esters are formed in high yields and excellent diastereoselectivities. An asymmetric version was also developed by employing chiral α-methylbenzyl imines as dipolarophiles yielding enantiomerically pure syn-α-hydroxy-β-amino esters. This methodology was also applied on a short asymmetric synthesis of the paclitaxel side-chain as well as in an asymmetric synthetic approach towards the proteasome inhibitor omuralide. Furthermore, the use of chiral Rh(II) carboxylates furnishes the syn-α-hydroxy-β-amino esters in moderate enantioselectivity (er up to 82:18), which indicates that the reaction proceeds via a metal-associated carbonyl ylide.

The second part describes the development of a 1,3-dipolar cycloaddition reaction of azomethine ylides to aldehydes for the synthesis of α-amino-β-hydroxy esters. Different methods for the generation of the ylides, including Vedejs’ oxazole methology and an Ag(I)/phosphine-catalyzed approach have been evaluated. The best results were obtained with the Ag(I)/phosphine approach, which yielded the desired α-amino-β-hydroxy ester in 68% yield and 3.4:1 syn:anti-selectivity.

The last two parts deals with the total synthesis of the amino alcohol-containing natural products D-erythro-sphingosine and (−)-stemoamide. The key transformation in the sphingosine synthesis is a cross-metathesis reaction for the assembly of the polar head group and the aliphatic chain. In the stemoamide synthesis, the key feature is an iodoboration/Negishi/RCM-sequence for the construction of the β,γ-unsaturated azepine core of stemoamide followed by a stereoselective bromolactonization/1,4-reduction strategy for the installation of the requisite C8-C9 trans-stereochemistry.

Place, publisher, year, edition, pages
Stockholm: KTH, 2007. 71 p.
Series
Trita-CHE-Report, ISSN 1654-1081 ; 2007:52
Keyword
Amino alcohol, asymmetric 1.3-dipolar cycloaddition, azomethine ylide, carbenoid, carbonyl ylide, cross-metathesis, omuralide, oxazolidine, rhodium, sphingosine, stemoamide, stereoselective synthesis, total synthesis.
National Category
Organic Chemistry
Identifiers
urn:nbn:se:kth:diva-4472 (URN)978-91-7178-734-7 (ISBN)
Public defence
2007-09-14, F3, Lindstedtsvägen 26, Stockholm, 10:00
Opponent
Supervisors
Note
QC 20100820Available from: 2007-08-23 Created: 2007-08-23 Last updated: 2010-08-20Bibliographically approved

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