The Theodorakis Synthesis of (–)-Jiadifenolide

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Hydrogen Peroxide ◽  
Carboxylic Acid ◽  
Aldol Condensation ◽  
University Of California ◽  
Oxidative Rearrangement ◽  
Promote Neurite Outgrowth ◽  
Starting Point ◽  
Jones Reagent ◽  
Acid Catalyzed ◽  
The University

There has recently been a great deal of interest in the synthesis of natural products that promote neurite outgrowth. Emmanuel A. Theodorakis of the University of California, San Diego described (Angew. Chem. Int. Ed. 2011, 50, 3672) the preparation of one of the most potent (10 nM) of these, (–)-jiadifenolide 3. Fittingly, a key transformation en route to this highly oxygenated seco-prezizaane was the oxidative rearrangement of 1 to 2. The starting point for the synthesis was the commercially available diketone 4. Allylation followed by addition to 5 gave the prochiral triketone 6. Enantioselective aldol condensation following the Tu/Zhang protocol then delivered the bicyclic enone 7. Alkylation to give 8 proceeded with high diastereoselectivity, perhaps controlled by the steric bulk of the silyloxy group. Exposure of the protected ketone to the McMurry reagent PhNTf2 gave the enol triflate 9, which smoothly carbonylated to the lactone 10. Epoxidation with alkaline hydrogen peroxide followed by oxidation gave the carboxylic acid, which spontaneously opened the epoxide, leading to the bis lactone 1. With 1 in hand, the stage was set for the key oxidative rearrangement to 2. It was envisioned that epoxidation would generate the cis-fused 11, which on oxidation would undergo acid-catalyzed elimination to give 12. The newly freed OH would then be in position to engage the lactone carbonyl, leading to 2. In the event, oxidation of the epoxide with the Dess-Martin reagent required sonication for 2 h. The rearranged lactone, even though it was susceptible to further oxidation, was secured in 38% overall yield from 1. After hydrogenation and protection, preparation of the enol triflate 13 from the congested cyclopentanone necessitated the use of the more reactive Comins reagent. Hydrogenation of the trisubstituted alkene from coupling with Me3Al then required 90 atmospheres of H2 overpressure. Hydroxylation of the lactone 14 with the Davis oxaziridine followed by further oxidation to the ketone with the Jones reagent and deprotection then completed the synthesis of (–)-jiadifenolide 3.

The Zakarian Synthesis of ( + )-Pinnatoxin A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Claisen Rearrangement ◽  
Aldol Condensation ◽  
Primary Alcohol ◽  
Allylic Alcohol ◽  
University Of California ◽  
Santa Barbara ◽  
Enantiomerically Pure ◽  
Calcium Channel Activator ◽  
The University ◽  
Nabh4 Reduction

( + )-Pinnatoxin A 3, isolated from the shellfish Pinna muricata, is thought to be a calcium channel activator. A key transformation in the synthesis of 3 reported (J. Am. Chem. Soc . 2008, 130, 3774) by Armen Zakarian, now at the University of California, Santa Barbara, was the diastereoselective Claisen rearrangement of 1 to 2. The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The absolute configuration of the secondary allylic alcohol was established by chiral amino alcohol catalyzed addition of diethyl zinc to the unsaturated aldehyde 5. The acid portion of the ester 1 was prepared from (S)-citronellic acid, by way of the Evans imide 7. Methylation proceeded with high diasterocontrol, to give 8. Functional group manipulation provided the imide 9. Alkylation then led to 10, again with high diastereocontrol. In each case, care had to be taken in the further processing of the α-chiral acyl oxazolidinones. Direct NaBH4 reduction of 8 delivered the primary alcohol. To prepare the acid 10, the alkylated acyl oxazolidinone was hydrolyzed with alkaline hydrogen peroxide. On exposure of the ester 1 to the enantiomerically-pure base 11, rearrangement proceeded with high diastereocontrol, to give the acid 2. This outcome suggests that deprotonation proceeded to give the single geometric form of the enolate, that was then trapped to give specifically the ketene silyl acetal 12. This elegant approach is dependent on both the ester 1 and the base 11 being enantiomerically pure. The carbocyclic ring of pinnatoxin A 3 was assembled by intramolecular aldol condensation of the dialdehyde 11. This outcome was remarkable, in that 11 is readily epimerizable, and might also be susceptible to β-elimination. Note that the while the diol corresponding to 11 could be readily oxidized to 11 under Swern conditions, attempts to oxidize the corresponding hydroxy aldehyde were not fruitful.

The Bergman-Ellman Synthesis of (-)-Incarvillateine

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
High Temperature ◽  
Ferulic Acid ◽  
Bond Formation ◽  
Reductive Elimination ◽  
University Of California ◽  
Enantiomerically Pure ◽  
Single Diastereomer ◽  
Symmetry Properties ◽  
Starting Point ◽  
The University

The monoterpene alkaloid (-)-incarvillateine 3 has interesting symmetry properties. The central cyclobutane diacid core is not itself chiral, but the appended alkaloids are. The key step in the total synthesis of 3 recently (J. Am. Chem. Soc. 2008, 130, 6316) described by Robert G. Bergman and Jonathan A. Ellman of the University of California, Berkeley was the diastereoselective Rh-catalyzed cyclization of 1 to 2. The cyclobutane diacid core 5 was assembled from ferulic acid 4 following the procedure of Kibayashi (J. Am. Chem. Soc. 2004, 126, 16553). The starting point for the preparation of 1 was the commercial aldehyde 6. Enantioselective allylation followed by silylation delivered 7, which on cross metathesis with methacrolein gave the diene aldehyde 8. Imine formation then completed the construction of 1. The cyclization of 1 was effected by warming (45 °C, 6 h) with 2.5 mol % [RhCl(coe)2]2 and 5.5 mol % (DMAPh)Pet2 ligand. While eight products were possible from the cyclization (four diastereomers, two geometric isomers of the exo alkene), only two were observed, with one predominating. Since the product mixture was easily susceptible to tautomerization, it was carried on directly to reduction and cyclization, to form the lactam 8. Hydrogenation of 8 to 9 required high temperature and pressure, but delivered 9 as a single diastereomer. Reduction and desilylation then set the stage for Mitsunobu coupling with 5, to give 11. Dissolving metal conditions removed the tosyl groups from 5 to give (-)-incarvillateine 3. It will be interesting to see how general this Rh catalyzed cyclization will be. It will also be interesting to establish the mechanism. The authors described the cyclization of 1 as proceeding via initial metalation of the alkene C-H bond, followed by insertion of the ester-bearing alkene into the C-Rh bond to form a new C-Rh bond, and finally reductive elimination. Their previous observation of metalation of such an unsaturated imine with maintenance of the alkene geometry suppported this mechanism. The high diastereocontrol also suggested intramolecular C-C bond formation. Whatever the mechanism, the enantiomerically-pure cyclopentane 2, having four of its five carbons functionalized, is a versatile intermediate for further transformation.

Dialogues

2020 ◽  
Vol 2 (3) ◽  
pp. 53-59
Keyword(s):  
Los Angeles ◽  
New Spain ◽  
American Art ◽  
Historical Trauma ◽  
State Building ◽  
University Of California ◽  
Religious Experiences ◽  
Political Space ◽  
California Missions ◽  
The University

The California missions, whose original church spaces and visual programs were produced by Iberian, Mexican, and Native artisans between 1769 and 1823, occupy an ambiguous chronological, geographical, and political space. They occupy lands that have pertained to conflicting territorialities: from Native nations, to New Spain, to Mexico, to the modern multicultural California. The physical and visual landscapes of the missions have been sites of complex and often incongruous religious experiences; historical trauma and romantic vision; Indigenous genocide, exploitation, resistance, and survivance; state building and global enterprise. This Dialogues section brings together critical voices, including especially the voices of California Indian scholars, to interrogate received models for thinking about the art historical legacies of the California missions. Together, the contributing authors move beyond and across borders and promote new decolonial strategies that strive to be responsive to the experience of California Indian communities and nations. This conversation emerges from cross-disciplinary relationships established at a two-day conference, “‘American’ Art and the Legacy of Conquest: Art at California’s Missions in the Global 18th–20th Centuries,” sponsored by the Terra Foundation for American Art and held at the University of California, Los Angeles, in November 2019.

Appraising Newness: Whiteness, Neoliberalism & the Building of the Archive for New Poetry

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Eunsong Kim
Keyword(s):  
San Diego ◽  
University Of California ◽  
Collection Development ◽  
Literary Scholarship ◽  
Avant Garde ◽  
Archival Practice ◽  
Small Press ◽  
The University

The Archive for New Poetry (ANP) at the University of California San Diego was founded with the specific intention of collecting alternative, small press publications and acquiring the manuscripts of contemporary new poets. The ANP’s stated collection development priority was to acquire alternative, non-mainstream, emerging, “experimental” poets as they were writing and alive, and to provide a space in which their papers could live, along with recordings of their poetry readings. In this article, I argue that through racialized understandings of innovation and new, whiteness positions the ANP’s collection development priority. I interrogate two main points in this article: 1) How does whiteness—though visible and open—remain unquestioned as an archival practice? and 2) How are white archives financed and managed? Utilizing the ANP’s financial proposals, internal administrative correspondences, and its manuscript appraisals and collections, I argue that the ANP’s collection development priority is racialized, and this prioritization is institutionally processed by literary scholarship that linked innovation to whiteness. Until very recently, US Experimental and “avant-garde” poetry has been indexed to whiteness. The indexing of whiteness to experimentation, or the “new” can be witnessed in the ANP’s collection development priorities, appraisals, and acquisitions. I argue that the structure of the manuscripts acquired by the ANP reflect literary scholarship that theorized new poetry as being written solely by white poets and conclude by examining the absences in the Archive for New Poetry.

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