New cyclic 2,3‐sulfite ester derivatives of poststerone—Discriminating diastereomers and probing spatial proximities by NMR and DFT calculations

Balázs, Attila; Hunyadi, Attila; Csábi, József; Tillekeratne, L. M. V.; Martins, Ana; Tóth, Gábor

doi:10.1002/mrc.4641

“…Further, all the compounds showed an increased potency as inhibitors of the ABCB1 transporter, commonly referred to as P-glycoprotein (Pgp) [7]. In contrast with the diacetonide, we found the sidechain cleaved ecdysteroid derivative poststerone to form cyclic sulfite esters that were only moderately active against some cancer cell lines [8].…”

Section: Introductionmentioning

confidence: 84%

“…Poststerone is known as a natural metabolite of 20-hydroxyecdysone, the most abundant ecdysteroid existing in nature, and thus, it can be straightforwardly obtained in larger quantities from the oxidative side-chain cleavage of the parent compound [9]. To facilitate antitumor properties, poststerone (8) was also further converted to its corresponding 2,3-acetonide derivative (9).…”

Section: Preparation Of Starting Materials For Reactions With Dastmentioning

confidence: 99%

Diversity-Oriented Synthesis Catalyzed by DAST – Preparation of New Antitumor Ecdysteroid Derivatives

Vágvölgyi¹,

Kocsis²,

Nové³

et al. 2022

Preprint

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Fluorine represents a privileged building block in pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination and cyclic Beckmann-rearrangement type reactions. In this work we aimed to use DAST for diversity-oriented semisynthetic transformation of natural products bearing multiple hydroxyl groups to prepare new bioactive compounds. Four ecdysteroids, including a new constituent of Cyanotis arachnoidea, were selected as starting materials for DAST-catalyzed transformations. The newly prepared compounds represented combinations of various structural changes DAST was known to catalyze, and a unique cyclopropane ring closure that was found for the first time. Several compounds demonstrated in vitro antitumor properties. A new 17-N-acetylecdysteroid (13) exerted potent antiproliferative activity and no cytotoxicity on drug susceptible and multi-drug resistant mouse T-cell lymphoma cells. Further, compound 13 acted in significant synergism with doxorubicin without detectable direct ABCB1 inhibition. Our results demonstrate that DAST is a versatile tool for diversity-oriented synthesis to expand chemical space towards new bioactive compounds.

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“…Further, all the compounds showed an increased potency as inhibitors of the ABCB1 transporter, commonly referred to as P-glycoprotein (Pgp) [ 9 ]. In contrast with the diacetonide, we found the sidechain cleaved ecdysteroid derivative poststerone to form cyclic sulfite esters that were only moderately active against some cancer cell lines [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Diversity-Oriented Synthesis Catalyzed by Diethylaminosulfur-Trifluoride—Preparation of New Antitumor Ecdysteroid Derivatives

Vágvölgyi

¹

,

Kocsis

²

,

Nové

³

et al. 2022

IJMS

Self Cite

1

0

View full text Add to dashboard Cite

Fluorine represents a privileged building block in pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination and cyclic Beckmann-rearrangement type reactions. In this work we aimed to use DAST for diversity-oriented semisynthetic transformation of natural products bearing multiple hydroxyl groups to prepare new bioactive compounds. Four ecdysteroids, including a new constituent of Cyanotis arachnoidea, were selected as starting materials for DAST-catalyzed transformations. The newly prepared compounds represented combinations of various structural changes DAST was known to catalyze, and a unique cyclopropane ring closure that was found for the first time. Several compounds demonstrated in vitro antitumor properties. A new 17-N-acetylecdysteroid (13) exerted potent antiproliferative activity and no cytotoxicity on drug susceptible and multi-drug resistant mouse T-cell lymphoma cells. Further, compound 13 acted in significant synergism with doxorubicin without detectable direct ABCB1 inhibition. Our results demonstrate that DAST is a versatile tool for diversity-oriented synthesis to expand chemical space towards new bioactive compounds.

show abstract