Total Synthesis of (+)-Strongylophorines 2 and 9

Dethe, Dattatraya H.; Sau, Susanta Kumar

doi:10.1021/acs.orglett.9b01254

Cited by 12 publications

(8 citation statements)

References 46 publications

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“…To complete our studies, we turned our attention toward some directed oxidation methods. [29] To begin with, we investigated the Suárez oxidation protocol [30] employing alcohol 17. Under these conditions, the C-20 iodide 25 was obtained in 28 % yield as the sole product.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis and Late‐Stage C−H Oxidations of ent‐Trachylobane Natural Products

2021

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Herein, we present our studies to construct seven ent-trachylobane diterpenoids by employing a bioinspired two-phase synthetic strategy. The first phase provided enantioselective and scalable access to five ent-trachylobanes, of which methyl ent-trachyloban-19-oate was produced on a 300 mg scale. During the second phase, chemical CÀ H oxidation methods were employed to enable selective conversion to two naturally occurring higher functionalized enttrachylobanes. The formation of regioisomeric analogs, which are currently inaccessible via enzymatic methods, reveals the potential as well as limitations of established chemical CÀ H oxidation protocols for complex molecule synthesis.

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Section: Methodsmentioning

confidence: 99%

Total Synthesis and Late‐Stage C−H Oxidations of ent‐Trachylobane Natural Products

2021

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“…2 Recently, an alternative route to ent-STR-9/ ent-STR-2 from the Wieland−Mischer ketone was reported by Dethe and Sau. 34 The overall approach to vinylogous esters that we adopted for the synthesis of STR-26 (3) is unique for the quinone system present, although related processes in standard Michael acceptor systems (oxa-Michael addition → enolate quenching with a halogenation agent → dehydrohalogention) can also be used for the preparation of vinylogous esters. Another common approach involves the enolization of 1,3-dicarbonyl groups and subsequent O-alkylation, as demonstrated in the synthesis of garuganin III (Figure 1B).…”

Section: ■ Semisyntheses Of the Strongylophorinesmentioning

confidence: 99%

“…While this ultimately allowed us to make STR-26 ( 3 ), along with a putative regioisomer ( 50 ) that we were not able to cleanly isolate, the identified catalytic conditions could be employed to effect a series of direct oxidative functionalizations of simple quinones with alcohol, amine, and thiol nucleophiles . Recently, an alternative route to ent -STR-9/ ent -STR-2 from the Wieland–Mischer ketone was reported by Dethe and Sau …”

Section: Semisyntheses Of the Strongylophorinesmentioning

confidence: 99%

Total Synthesis of Natural Products Containing Enamine or Enol Ether Derivatives

Poulsen

2021

Acc. Chem. Res.

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Conspectus Enamine and enol ethers are nucleophilic functional groups that are well known to most chemists. When enamine or enol ethers are present in natural products, they are nearly exclusively found as derivatives having a direct connection to electron-withdrawing groups for stabilization, and the resulting larger entities, such as enamides or enol acylates, can be further extended or modified in the framework of natural products. The restricted conformational space that is associated with even simple enamine and enol ether derivatives can be a strong determinant of the overall molecular structure, and the more polarized derivatives can endow some natural products with electrophilic properties and thus facilitate covalent interactions with biological targets. In this Account, I describe our efforts (published since 2016) to prepare natural products from several different classes that all feature enamine or enol ether derivatives as key functionalities. Our choice of targets has been guided by a desire to illuminate unknown biological mechanisms associated with the compounds or, alternatively, to improve upon known biological activities that appear to be promising from a biomedical perspective. In the present text, however, the exclusive focus will be on the syntheses. First, I will discuss the basic properties of the functional groups and briefly present a small collection of illustrative and inspirational examples from the literature for their construction in different complex settings. Next, I will provide an overview of our work on the macrocyclic APD-CLD natural products, rakicidin A and BE-43547A1, involving the development of an efficient macrocyclization strategy and the development of methods to construct the hallmark APD group: a modified enamide. The synthesis of the meroterpenoid strongylophorine-26 is discussed next, where we developed an oxidative quinone methoxylation to build a vinylogous ester group in the final step of the synthesis and employed FeCl3-mediated cascade reactions for the rapid assembly of the overall scaffold to enable a short semisynthesis from isocupressic acid. An efficient core scaffold assembly was also in focus in our synthesis of the alkaloid streptazone A with the signature enaminone system being assembled through a rhodium-catalyzed Pauson–Khand reaction. Sequential, site-selective redox manipulations were developed to arrive at strepatzone A and additional members of the natural product family. Finally, I discuss our work to prepare analogs of complex polyether ionophores featuring functionalized tetronic acids as cation-binding groups. A method for the construction of a suitably protected chloromethylidene-modified tetronate is presented which enabled its installation in the full structure through a C-acylation reaction. This work exemplifies how components of abundant polyether ionophores can be recycled and used to access new structures which may possess enhanced biological activities.

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“…In the course of our work on bioactive natural products and bioactive materials [117][118][119][120][121][122][123][124], it occurred to us to observe the partial racemization of (+)-5 during the acetalization of (+)-1 with 1,2-ethanediol and TsOH in the presence of a Dean-Stark apparatus. According to our best knowledge, obtaining partially racemized (+)-5 or (−)-5 when the acetalization reaction is carried out by this procedure on (+)-1 or (-)-1 [33,35,39,40,44,48,49,72,77,81,84,[87][88][89][90][91]116], respectively, has not been previously reported in the literature, which was the reason behind investigating this reaction.…”

Section: Introductionmentioning

confidence: 96%

Unexpected Racemization in the Course of the Acetalization of (+)-(S)-5-Methyl-Wieland–Miescher Ketone with 1,2-Ethanediol and TsOH under Classical Experimental Conditions

Leonelli

Piergentili

Lucarelli

et al. 2019

IJMS

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(+)-(S) and (−)-(R)-5-methyl-Wieland-Miescher ketone (+)-1 and (−)-1, are important synthons in the diastereo and enantioselective syntheses of biological and/or pharmacological interesting compounds. A key step in these syntheses is the chemoselective C(1)O acetalization to (+)-5 and (−)-5, respectively. Various procedures for this transformation have been described in the literature. Among them, the classical procedure based on the use of 1,2-ethanediol and TsOH in refluxing benzene in the presence of a Dean-Stark apparatus. Within our work on bioactive natural products, it occurred to us to observe the partial racemization of (+)-5 in the course of the acetalization of (+)-1 by means of the latter methodology. Aiming to investigate this drawback, which, to our best knowledge, has no precedents in the literature, we acetalized with 1,2-ethanediol and TsOH in refluxing benzene and in the presence of a Dean–Stark apparatus under various experimental conditions, enantiomerically pure (+)-1. It was found that the extent of racemization depends on the TsOH/(+)-1 and 1,2-ethanediol/(+)-1 ratios. Mechanism hypotheses for this partial and unexpected racemization are provided.

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Total Synthesis of (+)-Strongylophorines 2 and 9

Cited by 12 publications

References 46 publications

Total Synthesis and Late‐Stage C−H Oxidations of ent‐Trachylobane Natural Products

Total Synthesis and Late‐Stage C−H Oxidations of ent‐Trachylobane Natural Products

Total Synthesis of Natural Products Containing Enamine or Enol Ether Derivatives

Unexpected Racemization in the Course of the Acetalization of (+)-(S)-5-Methyl-Wieland–Miescher Ketone with 1,2-Ethanediol and TsOH under Classical Experimental Conditions

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