Reactions of vinylogous phosphonate carbanions and Reformatskii reagents with a sterically hindered ketone and enone

Robinson, Cynthia Y.; Brouillette, Wayne J.; Muccio, Donald D.

doi:10.1021/jo00269a045

Cited by 12 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some key points of the synthesis are reported here. Unlike previous reports, , a δ-lactone intermediate was not detected but was assumed to be an intermediate in the production of (9 Z )- 2 . (9 Z )- 5 and (9 Z ,13 Z )- 5 were preparatively separated by HPLC on silica gel (0.5% Et 2 O, 0.1% THF in hexane) using methods similar to those we previously described. ,, Individual isomers of ester 5 were hydrolyzed to the corresponding acids in KOH, without E / Z -isomerization .…”

Section: Chemistrycontrasting

confidence: 64%

“…Since Horner−Emmons condensations on 2-cyclohexenone gave only 1,4-addition products, we first generated ester 7 , a dihydro precursor to UAB1. This was accomplished using a Horner−Emmons condensation between cyclohexanone and diethyl 3-(ethoxycarbonyl)-2-methylprop-2-enylphosphonate, which we previously reported in modest yield during a reactivity study . The modified procedure described here utilized HMPA as cosolvent, produced much higher yields, and gave nearly exclusively (9 E) - 7 .…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Conformationally Defined 6-s-trans-Retinoic Acid Analogs. 3. Structure−Activity Relationships for Nuclear Receptor Binding, Transcriptional Activity, and Cancer Chemopreventive Activity

et al. 1996

Self Cite

View full text Add to dashboard Cite

We recently demonstrated that conformationally defined 6-s-trans-retinoic acid (RA) analogs were effective in the prevention of skin papillomas (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) and selective agonists for nuclear receptor binding and activation (Alam et al. J. Med. Chem. 1995, 38, 2302-2310). In order to probe important structure-activity relationships, we evaluated a homologous series of four 6-s-trans-retinoids that are 8-(2'-cyclohexen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acids with different substituents at 2' (R2) and 3' (R1) positions on the cyclohexene ring. UAB1 (R1 = R2 = H), UAB4 (R1 = R2 = Me), UAB7 (R1 = Me, R2 = iPr), and UAB8 (R1 = Et, R2 = iPr) contain alkyl R groups that mimic, to different extents, portions of the trimethylcyclohexenyl ring of RA. Both 9Z- and all-E-isomers of these retinoids were evaluated in binding assays for cellular retinoic acid-binding proteins (CRABP-I and CRABP-II), a nuclear retinoic acid receptor (RAR alpha), and a nuclear retinoid X receptor (RXR alpha). The all-E-isomers of UAB retinoids bound tightly to CRABPs and RAR alpha, the binding affinity of the all-E-isomer increased systematically from UAB1 to UAB8, and binding for the latter was comparable to that of all-E-RA. In contrast to RA, the (9Z)-UAB retinoids were at least 200-fold less active than the all-E-isomers in binding to RAR alpha. The (9Z)-UAB isomers exhibited increasingly stronger binding to RXR alpha, and (9Z)-UAB8 was nearly as effective as (9Z)-RA in binding affinity. The retinoids were also evaluated in gene expression assays mediated by RAR alpha and RXR alpha homodimers or RAR alpha/RXR alpha heterodimers. Consistent with the binding affinities, the (all-E)-UAB retinoids activated gene transciption mediated by RAR alpha homodimers or RAR alpha/RXR alpha heterodimers, while the (9Z)-UAB isomers activated only the RXR alpha homodimer-mediated transcription. The all-E- and 9Z-isomers of the UAB retinoids were further evaluated for their capacity to prevent the induction of mouse skin papillomas. When compared to RA, only the (all-E)-UAB retinoids containing bulky R1 and R2 groups were effective in this chemoprevention assay. (9Z)-RA displayed equal capacity as RA to prevent papillomas, while the 9Z-isomers of the UAB retinoids were much less effective. Taken together, these studies demonstrate that the cyclohexenyl ring substituents of 6-s-trans-UAB retinoids are important for their biological activities and that the chemopreventive effect of the all-E-isomers of these retinoids correlates well with their capacity to bind to RARs and activate RAR/RXR-mediated transcription.

show abstract

Section: Chemistrycontrasting

confidence: 64%

Section: Chemistrymentioning

confidence: 99%

Conformationally Defined 6-s-trans-Retinoic Acid Analogs. 3. Structure−Activity Relationships for Nuclear Receptor Binding, Transcriptional Activity, and Cancer Chemopreventive Activity

et al. 1996

Self Cite

View full text Add to dashboard Cite

show abstract

“…Then transition metal-catalyzed cross-coupling reactions galvanized the synthesis of these complex conjugated molecules. Catalysts such as ruthenium [4], zirconium [5][6][7], zinc [8] and nickel [9] were successfully used. The use of palladium has been widely reported with 2 of 9 Negishi [10,11], Stille [12][13][14][15], Suzuki-Miyaura [16][17][18], Sonogashira [19], Kumada-Tamao [20] and Mizoroki-Heck [21][22][23][24][25] cross-coupling reactions [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Solvent-Free Mizoroki-Heck Reaction Applied to the Synthesis of Abscisic Acid and Some Derivatives

2018

View full text Add to dashboard Cite

Abscisic acid (ABA) is a natural product, which is a well-known phytohormone. However, this molecule has recently exhibited interesting biological activities, emphasizing the need for a simple and direct access to new analogues based on the ABA framework. Our strategy relies on a pallado-catalyzed Mizoroki-Heck cross-coupling as key reaction performed in solvent and ligand free conditions. After a careful optimization, we succeeded in accessing various (E/Z)-dienes and (E/E/Z)-trienes in moderate to good yields without isomerization and applied the same approach to the synthesis of ABA in an environmentally sound manner.

show abstract

“…The base-promoted Horner−Wadsworth−Emmons olefination of aldehydes and ketones with trialkyl 4-phosphonocrotonates , has found frequent use for the preparation of 2,4-dienoates, and a variety of bases, including NaH, − LDA, − and LiHMDS, − have been commonly employed. However, for some of the dienoates we needed, these conditions proved to be unsatisfactory.…”

mentioning

confidence: 99%

“…The dienylation of cyclohexanone has been reported in the literature, and the comparison to those results again highlights the advantage of this method over earlier procedures. Robinson and co-workers reported that the reaction of cyclohexanone with triethyl 4-phosphonocrotonate using NaH as the base (THF−HMPA, 25 °C) afforded the dienoate in only 32% yield …”

mentioning

confidence: 99%

A Useful Procedure for the Preparation of (E,E)-2,4-Dienoates: Lithium Hydroxide-Promoted Dienylation by 4-Phosphonocrotonate

et al. 1998

View full text Add to dashboard Cite

Reactions of vinylogous phosphonate carbanions and Reformatskii reagents with a sterically hindered ketone and enone

Cited by 12 publications

References 0 publications

Conformationally Defined 6-s-trans-Retinoic Acid Analogs. 3. Structure−Activity Relationships for Nuclear Receptor Binding, Transcriptional Activity, and Cancer Chemopreventive Activity

Conformationally Defined 6-s-trans-Retinoic Acid Analogs. 3. Structure−Activity Relationships for Nuclear Receptor Binding, Transcriptional Activity, and Cancer Chemopreventive Activity

Solvent-Free Mizoroki-Heck Reaction Applied to the Synthesis of Abscisic Acid and Some Derivatives

A Useful Procedure for the Preparation of (E,E)-2,4-Dienoates: Lithium Hydroxide-Promoted Dienylation by 4-Phosphonocrotonate

Contact Info

Product

Resources

About