Identification and Total Synthesis of an Unstable Anticancer Macrolide Presaccharothriolide Z Produced by <i>Saccharothrix</i> sp. A1506

Kuranaga, Takefumi; Tamura, Miho; Ikeda, Hiroaki; Terada, Sakahiro; Nakagawa, Yusuke; Kakeya, Hideaki

doi:10.1021/acs.orglett.1c02506

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Regarding the synthesis of alcohol 21 , we anticipated that construction of the 10-membered lactone ring would be one of the most challenging transformations to achieve, given the general difficulty of forming medium-sized rings . Additionally, in our case, the tri-substituted double bond in the 10-membered lactone of 21 could cause even more strain in the ring (see the Supporting Information, Figure S1).…”

Section: Resultsmentioning

confidence: 99%

Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin

et al. 2022

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This article describes the first total synthesis of luminamicin using a strategy combining chemical degradation with synthesis. Chemical degradation studies provided a sense of the inherent reactivity of the natural product, and deconstruction of the molecule gave rise to a key intermediate, which became the target for chemical synthesis. The core structure of the southern part of luminamicin was constructed by a 1,6-oxa-Michael reaction to form an oxa-bridged ring, followed by coupling with a functionalized organolithium species. Modified Shiina macrolactonization conditions forged the strained 10-membered lactone containing a tri-substituted olefin. Diastereoselective α-oxidation of the 10-membered lactone completed the center part to provide the key intermediate. Inspired by the degradation study, an unprecedented enol ether/maleic anhydride moiety was constructed with a one-pot chlorosulfide coupling and thiol β-elimination sequence. Finally, macrolactonization to the 14-membered ring in the presence of the highly electrophilic maleic anhydride moiety was accomplished using modified Mukaiyama reagents to complete the synthesis of luminamicin.

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Section: Resultsmentioning

confidence: 99%

Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin

et al. 2022

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“…The genus possesses the ability to produce antibiotic substances such as dithiolopyrrolone [8] and saccharobipyrimicin [9]. Recently, the genus was reported to produce unstable anticancer macrolide presaccharothriolide Z [10]. Saccharothrix species are aerobic, Gram-stain-positive actinomycetes and characterized by fragmentation of both the vegetative and aerial mycelia into non-motile rods and ovoid elements.…”

Section: Full-textmentioning

confidence: 99%

Saccharothrix luteola sp. nov., a novel cellulose-degrading actinobacterium isolated from soil and emended description of the genus Saccharothrix

Sun

Huang

et al. 2022

International Journal of Systematic and Evolutionary Microbiology

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A novel cellulose-degrading actinobacterium, designated strain NEAU-S10T, was isolated from soil collected from Chifeng, Inner Mongolia Autonomous Region, PR China, and characterized using a polyphasic approach. Pairwise similarity of the 16S rRNA gene sequence showed that strain NEAU-S10T was a representative of Saccharothrix and was closely related to Saccharothrix carnea NEAU-yn17T (99.2 %), Saccharothrix saharensis SA152T (99.0 %), Saccharothrix texasensis DSM 44231T (98.5 %) and Saccharothrix xinjiangensis NBRC 101911T (98.5 %). Physiological and chemotaxonomic characteristics of the strain further supported its affiliation to the genus Saccharothrix . The whole-cell sugars contained galactose, ribose and mannose. The polar lipids contained diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The predominant menaquinones were MK-9(H0), MK-9(H2), MK-9(H4) and MK-10(H4). The major fatty acids were iso-C16 : 0, C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C17 : 0. The genomic DNA G+C content was 71.8 mol%. The levels of digital DNA–DNA hybridization between isolate and S. carnea NEAU-yn17T, S. saharensis SA152T and S. texasensis DSM 44231T were 40.1 % (37.6–42.6 %), 38.soap8 % (36.3–41.3 %) and 44.8 % (42.2–47.3 %) and the ANI values between them were determined to be 90.2, 89.8 and 91.7 %, the results indicated that strain NEAU-S10T could be distinguished from its reference strains. The assembled genome sequence of strain NEAU-S10T was found to be 10 305 394 bp long. The NCBI Prokaryotic Genome Annotation Pipeline (PGAP) revealed 8 994 protein-coding genes. Genomic analysis and Congo red staining test indicated that strain NEAU-S10T had the potential to degrade cellulose. The genomic and phenotypic results indicate that strain NEAU-S10T represents a novel species of the genus Saccharothrix , for which the name Saccharothrix luteola sp. nov. is proposed, with NEAU-S10T (=CCTCC AA 2020037T=JCM 34800T) as the type strain.

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“…Notably, Kakeya and co-workers have recently developed several labeling reagents [ 54 ] inspired by the synthetic and structural studies on the peptidic natural products yaku’amides A and B [ 55 , 56 ]. These highly sensitive labeling reagents are useful for the structural determination of peptides [ 57 , 58 ] and identification of the scarce reactive natural products [ 59 ]. After the accomplished the total synthesis, the highly isomerizable structure of synthesized 22 was confirmed by utilizing their labeling reagents [ 60 ].…”

Section: Total Synthesis Of Thioamycolamide a Toward Understanding Th...mentioning

confidence: 99%

Total syntheses of surugamides and thioamycolamides toward understanding their biosynthesis

Kuranaga

2022

J Nat Med

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Peptidic natural products have received much attention as potential drug leads, and biosynthetic studies of peptidic natural products have contributed to the field of natural product chemistry over the past several decades. However, the key biosynthetic intermediates are generally not isolated from natural sources, and this can hamper a detailed analysis of biosynthesis. Furthermore, reported unusual structures, which are targets for biosynthetic studies, are sometimes the results of structural misassignments. Chemical synthesis techniques are imperative in solving these problems. This review focuses on the chemical syntheses of surugamides and thioamycolamides toward understanding their biosynthesis. These studies can provide the key biosynthetic intermediates that can reveal the biosynthetic pathways and/or true structures of these natural products. Graphical abstract

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Identification and Total Synthesis of an Unstable Anticancer Macrolide Presaccharothriolide Z Produced by Saccharothrix sp. A1506

Cited by 6 publications

References 35 publications

Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin

Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin

Saccharothrix luteola sp. nov., a novel cellulose-degrading actinobacterium isolated from soil and emended description of the genus Saccharothrix

Total syntheses of surugamides and thioamycolamides toward understanding their biosynthesis

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