Concise Formal Total Synthesis of Platensimycin Mediated by a Stereoselective Autoxidation and Hydroxyl Group Directed Conjugative Reduction

2010 ◽  
Vol 12 (24) ◽  
pp. 5677-5679 ◽  
Author(s):  
Philip Magnus ◽  
Heriberto Rivera ◽  
Vince Lynch
Keyword(s):  
Total Synthesis ◽  
Hydroxyl Group

Stereocontrol of Michael hydride reduction by a remote hydroxyl group. A strategy for stereorational total synthesis of spatane diterpenes

1984 ◽  
Vol 106 (7) ◽  
pp. 2211-2213 ◽  
Author(s):  
Robert G. Salomon ◽  
Navzer D. Sachinvala ◽  
Swadesh R. Raychaudhuri ◽  
Donald B. Miller
Keyword(s):  
Total Synthesis ◽  
Hydroxyl Group ◽  
Hydride Reduction ◽  
Group A

scholarly journals Studies on the Synthesis of Marine Natural Product (-)-Zampanolide and its Analogues

2021 ◽  
Author(s):  
◽  
Jingjing Wang
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Aldol Reaction ◽  
Marine Natural Product ◽  
Alternative Methods ◽  
Hydroxyl Group ◽  
Cancer Drug ◽  
Drug Candidate ◽  
Three Component Reaction ◽  
Potential Therapeutic Application

<p>(-)-Zampanolide is a microtubule-stabilising marine natural product, with promise as a cancer drug candidate. The potential therapeutic application of zampanolide has fuelled worldwide interest in its total synthesis, but few analogue studies have been reported. Analogues afford the possibility of examining the structure-activity relationships with a view to optimising for potency and medicinal viability. This project seeks to devise a new route to zampanolide and generate a series of analogues for bioactivity evaluation.   The initial approach to zampanolide and a number of designed analogues was through disconnections at C20 by an N-aldol reaction, at C1 by Yamaguchi esterification, at C8-C9 by metathesis and at C15-C16 by alkynylation. During the development of fragment syntheses, problems were encountered with protection of the secondary hydroxyl group at C19 and establishment of an aldehyde at C15. Useful natural and analogue fragments were generated during this exploratory phase.  The order of connections was revised, and effort has been put towards the improvement of the synthetic efficiency. A three-component reaction involving (triphenylphosphoranylidene)-ketene, also known as Bestmann ylide, as a linchpin was envisaged to provide the dienoate of zampanolide. This is an expanded application of Bestmann ylide and therefore the scope of this linchpin reaction was investigated using simple alcohols and aldehydes. Success in the scoping study fortified this approach, and the coupling of the C3-C8 and C16-C20 fragments of zampanolide proceeded with good yields and stereoselectivity of the E,Z-geometry.  The planned late stage connections were tested on model substrates. The side arm attachment by a chiral boron reagent-promoted aza-aldol reaction failed to produce desired product on a simple model. However, model substrates that better account for the functionality of the zampanolide macrocycle are proposed for subsequent studies. In case these also do not succeed, reliable alternative methods described in the literature would be used. Several methods were scanned for the asymmetric alkynylation required for the C15-C16 bond connection. That involving ProPhenol and diethylzinc produced an excellent yield with a model alkyne. Although the stereoselectivity of the alkynylation is yet to be optimized, it was also tested on the full zampanolide fragment generated from the Bestmann ylide reaction. A small amount of the desired product was isolated, establishing 16 out of the 18 carbons of the macrocycle. Formation of a macrocycle is close at hand.</p>

scholarly journals Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I

2020 ◽  
Author(s):  
Alexander Amatuni ◽  
Anton Shuster ◽  
Alexander Adibekian ◽  
Hans Renata
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Product Family ◽  
Enzymatic Oxidation ◽  
Hydroxyl Group ◽  
Cellular Targets ◽  
Structure Activity ◽  
Covalent Inhibitors

The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to prepare a key hydroxylated amino acid building block in a scalable fashion. The strategy developed herein enabled access to a chemoproteomic probe, which in turn revealed the exceptional selectivity and potency of cepafungin I towards the b2 and b5 subunits of the proteasome. Further structure-activity relationship studies suggest the key role of the hydroxyl group in the macrocycle and the identity of the lipid tail in modulating the potency of this natural product family. This study lays the groundwork for further medicinal chemistry exploration to fully realize the anticancer potential of cepafungin I. <br>

scholarly journals Studies on the Synthesis of Marine Natural Product (-)-Zampanolide and its Analogues

2021 ◽  
Author(s):  
◽  
Jingjing Wang
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Aldol Reaction ◽  
Marine Natural Product ◽  
Alternative Methods ◽  
Hydroxyl Group ◽  
Cancer Drug ◽  
Drug Candidate ◽  
Three Component Reaction ◽  
Potential Therapeutic Application

<p>(-)-Zampanolide is a microtubule-stabilising marine natural product, with promise as a cancer drug candidate. The potential therapeutic application of zampanolide has fuelled worldwide interest in its total synthesis, but few analogue studies have been reported. Analogues afford the possibility of examining the structure-activity relationships with a view to optimising for potency and medicinal viability. This project seeks to devise a new route to zampanolide and generate a series of analogues for bioactivity evaluation.   The initial approach to zampanolide and a number of designed analogues was through disconnections at C20 by an N-aldol reaction, at C1 by Yamaguchi esterification, at C8-C9 by metathesis and at C15-C16 by alkynylation. During the development of fragment syntheses, problems were encountered with protection of the secondary hydroxyl group at C19 and establishment of an aldehyde at C15. Useful natural and analogue fragments were generated during this exploratory phase.  The order of connections was revised, and effort has been put towards the improvement of the synthetic efficiency. A three-component reaction involving (triphenylphosphoranylidene)-ketene, also known as Bestmann ylide, as a linchpin was envisaged to provide the dienoate of zampanolide. This is an expanded application of Bestmann ylide and therefore the scope of this linchpin reaction was investigated using simple alcohols and aldehydes. Success in the scoping study fortified this approach, and the coupling of the C3-C8 and C16-C20 fragments of zampanolide proceeded with good yields and stereoselectivity of the E,Z-geometry.  The planned late stage connections were tested on model substrates. The side arm attachment by a chiral boron reagent-promoted aza-aldol reaction failed to produce desired product on a simple model. However, model substrates that better account for the functionality of the zampanolide macrocycle are proposed for subsequent studies. In case these also do not succeed, reliable alternative methods described in the literature would be used. Several methods were scanned for the asymmetric alkynylation required for the C15-C16 bond connection. That involving ProPhenol and diethylzinc produced an excellent yield with a model alkyne. Although the stereoselectivity of the alkynylation is yet to be optimized, it was also tested on the full zampanolide fragment generated from the Bestmann ylide reaction. A small amount of the desired product was isolated, establishing 16 out of the 18 carbons of the macrocycle. Formation of a macrocycle is close at hand.</p>

First total synthesis of quiquesetinerviusin A

2017 ◽  
Vol 41 (5) ◽  
pp. 296-300 ◽  
Author(s):  
Yamu Xia ◽  
Zhen Mo ◽  
Lin Sun ◽  
Lijia Zou ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Ester Group ◽  
Raw Material ◽  
Protecting Groups ◽  
Related Structure ◽  
Hydroxyl Group ◽  
Acid Ligand

The first total synthesis of the dihydrobenzofuran neolignan quiquesetinerviusin A and its related structure have been described. Phenolic coupling is the key step to constructing the dihydrobenzofuran skeleton with vanillin as the raw material. The hydroxyl group was protected with dihydropyran (DHP) and the ester group was reduced with diisobutylaluminium hydride (DIBAL-H) in order to obtain the crucial intermediate diol, which was then condensed with an acid ligand to give the desired compounds following removal of the protecting groups.

Synthetic Study towards the Total Synthesis of (+)-(6S,2'R)-Cryptocaryalactone

2014 ◽  
Vol 1033-1034 ◽  
pp. 576-578
Author(s):  
Fei Fei Huang ◽  
Dong Wang Liu ◽  
Lin Jun Tang ◽  
Li Ping Wang ◽  
Shuang Ping Huang ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Aldol Reaction ◽  
Hydroxyl Group

A concise route to total synthesis of (+)-(6S, 2'R)-cryptocaryalactone (1) was designed and the key intermediate (3) was synthesized via an Evans Aldol reaction to construct the chiral hydroxyl group.

First Total Synthesis of 3-Epi-calystegin B2

2011 ◽  
Vol 66 (3) ◽  
pp. 317-323
Author(s):  
René Csuk ◽  
Stefan Reißmann ◽  
Ralph Kluge ◽  
Dieter Ströhl ◽  
Claudia Korb
Keyword(s):  
Total Synthesis ◽  
Ring Opening ◽  
Tight Binding ◽  
Ring Closure ◽  
Hydroxyl Group ◽  
Target Compound ◽  
Metathesis Reaction ◽  
Ring Opening Reaction ◽  
Ultrasound Assisted ◽  
Key Steps

A straightforward chiral pool synthesis for a non-natural calystegin, 3-epi-B2, is described. Key steps of this synthesis include an ultrasound-assisted Zn-mediated tandem ring opening reaction followed by a Grubbs’ catalyst-mediated ring closure metathesis reaction. Compared to calystegin B2, the target compound is no longer an inhibitor for a β -glycosidase hence proving that an equatorial hydroxyl group at position C-3 is necessary for a tight binding of calystegins into the active site of β -glycosidases.

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