Synthetic Study on Pactamycin: Stereoselective Synthesis of the Cyclopentane Core Framework

Goto, Atsumi; Yoshimura, Satoshi; Nakao, Yuta; Inai, Makoto; Asakawa, Tomohiro; Egi, Masahiro; Hamashima, Yoshitaka; Kondo, Mitsuru; Kan, Toshiyuki

doi:10.1021/acs.orglett.7b01257

Cited by 22 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 2017, Kan published a unique desymmetrization strategy to form the racemic core of 1 (Scheme 4). [12a] The tertiary C5 and secondary C7 alcohols were proposed to arise through the derivatization of the acetal found in 4.11 . The challenging C1 urea of 4.11 would be formed via Curtius rearrangement at a late stage, allowing the well‐behaved methyl ester at C1 in 4.7 to be used throughout most of the synthesis.…”

Section: Syntheses Of the Core Of Pactamycinmentioning

confidence: 99%

Strategies for the Syntheses of Pactamycin and Jogyamycin

2021

View full text Add to dashboard Cite

Pactamycin and jogyamycin are aminocyclopentitol natural products, where each core carbon bears a stereodefined alcohol or amine moiety. Their structural complexity, coupled with the diversity of functional groups coexisting in a condensed space, make them fascinating synthetic targets in their own right. Pactamycin and its derivatives bind to the 30S ribosomal subunit and display activity against parasites responsible for drug‐resistant malaria and African sleeping sickness; however, efforts to develop their therapeutic potential have been hampered by their cellular toxicity. Interestingly, bioengineered analogues display differences in selectivity and toxicity towards mammalian cells, spurring efforts to develop flexible strategies to thoroughly probe structure–activity relationships (SAR), particularly in analogues lacking the C7 hydroxyl group of pactamycin. This review compares and contrasts approaches towards pactamycin and jogyamycin, including two successful total syntheses of the former. The implications of each route for preparing analogues to inform SAR and lead to compounds with increased selectivity for binding malarial over human ribosomes are briefly discussed.

show abstract

Section: Syntheses Of the Core Of Pactamycinmentioning

confidence: 99%

Strategies for the Syntheses of Pactamycin and Jogyamycin

2021

View full text Add to dashboard Cite

show abstract

“…Kan veröffentlichte 2017 eine einzigartige Desymmetrisierungsstrategie zur Bildung des racemischen Kerns von 1 (Schema 4). [12a] In der Retrosynthese wurde angenommen, dass der tertiäre C5‐ und der sekundäre C7‐Alkohol durch Derivatisierung als Acetal in 4.11 entstehen könnten. Die problematische C1‐Harnstoffgruppe von 4.11 könnte über Curtius‐Umlagerung an einer späteren Stelle gebildet werden, sodass der unproblematische Methylester an C1 in 4.7 in nahezu der gesamten Synthese vorliegen könnte.…”

Section: Synthesen Des Kerns Von Pactamycinunclassified

Strategien für die Synthese von Pactamycin und Jogyamycin

2021

View full text Add to dashboard Cite

Pactamycin und Jogyamycin sind Aminocyclopentitol‐Naturstoffe, deren Kohlenstoffkern stereochemisch definierte Alkohol‐ oder Amineinheiten trägt. Aufgrund ihrer strukturellen Komplexität sowie der Vielfältigkeit der funktionellen Gruppen auf engem Raum sind sie faszinierende Syntheseziele. Pactamycin und dessen Derivate binden zur ribosomalen 30S‐Untereinheit und zeigen Wirkung gegen Parasiten, die arzneimittelresistente Malaria und afrikanische Schlafkrankheit verursachen; jedoch wird die Weiterentwicklung ihres therapeutischen Potenzials durch zelluläre Toxizität gebremst. Interessanterweise zeigen biotechnologisch erzeugte Analoga Unterschiede in der Selektivität und Toxizität in Säugerzellen, was die Entwicklung flexibler Strategien zur genauen Untersuchung der Struktur‐Wirkungs‐Beziehungen (SARs), insbesondere von Pactamycinanaloga ohne C7‐Hydroxygruppe, anspornt. In diesem Aufsatz werden Ansätze zur Synthese von Pactamycin und Jogyamycin gegenübergestellt, einschließlich zweier Totalsynthesen von Pactamycin. Wir diskutieren kurz die Bedeutung jeder Syntheseroute zu Analoga für die Untersuchung von SARs und die Entwicklung von Verbindungen mit erhöhter Selektivität für die Bindung an Ribosomen des Malariaerregers anstelle menschlicher Ribosomen.

show abstract

“…121,122 The three contiguous quaternary stereogenic carbons of jogyamycin, as well as the dense functionalization around the ring that includes sensitive urea and aniline moieties, have inspired a number of strategies to achieve a total synthesis of this molecule. [131][132][133][134][135][136][137][138][139][140][141][142] However, these efforts have either been unsuccessful or do not allow for deep-seated changes to the core of the molecule, rendering any future explorations of structureactivity relationships challenging.…”

Section: Synthesis Of the Core Of Jogyamycinmentioning

confidence: 99%

Oxidative allene amination for the synthesis of nitrogen-containing heterocycles

Eshon¹,

Gerstner²,

Schomaker³

2018

Arkivoc

View full text Add to dashboard Cite

The prevalence of stereochemically complex amines in natural products, pharmaceuticals and other bioactive compounds, coupled with the challenges inherent in their preparation, has inspired work to develop new and versatile methodologies for the synthesis of amine-containing stereotriads ('triads'). The key step is a highly chemo-, regio-, and stereo-selective transition-metal catalyzed nitrene transfer reaction that transforms one of the cumulated double bonds of an allene precursor into a bicyclic methyleneaziridine intermediate. This account summarizes our strategies for elaboration of such intermediates into stereochemically rich, densely functionalized amine triads, nitrogen heterocycles, aminated carbocycles and other useful synthetic building blocks.

show abstract

Synthetic Study on Pactamycin: Stereoselective Synthesis of the Cyclopentane Core Framework

Cited by 22 publications

References 29 publications

Strategies for the Syntheses of Pactamycin and Jogyamycin

Strategies for the Syntheses of Pactamycin and Jogyamycin

Strategien für die Synthese von Pactamycin und Jogyamycin

Oxidative allene amination for the synthesis of nitrogen-containing heterocycles

Contact Info

Product

Resources

About