- A novel semi-synthesis of spinetoram-J based on the selective hydrolysis of 5,6-dihydro spinosyn A
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Spinetoram is a novel kind of fermentation-derived insecticide with a broad range of action against lots of insect pests. Due to the broad pest spectrum, high insecticidal activity, low environmental impact, and low toxicity to non-target species, spinetoram has been widely applied in pest control and stored-grain protection. Spinetoram is a mixture of spinetoram-J (XDE-175-J, major component) and spinetoram-L (XDE-175-L). In this study, a novel selective hydrolysis of C9-glycosidic bond of 5,6-dihydro spinosyn A was developed. And a 3-step semi-synthesis of spinetoram-J based on the selective hydrolysis was designed and discussed. All compounds in the synthesis were characterized by 1H NMR, 13C NMR and mass spectrum. In addition, the improved semi-synthesis also provides an efficient way to synthesize the rhamnose replacement analogues of spinetoram-J which may be promising in the pest control and fungus control. (Figure presented.).
- Zhang, Kai,Li, Jiarong,Lamusi
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- Synthesis and anti-OXPHOS, antitumor activities of DLC modified spinosyn derivatives
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A series of DLC (delocalized lipophilic cation) modified spinosyn derivatives were synthesized and evaluated for antitumor efficacies both in vitro and in vivo. Cancer cell based antiproliferative assays indicated that the more lipophilic derivatives had stronger inhibitory effects on the tested cancer cell lines. Compound 7b and 8b exhibited strong anti-OXPHOS and apoptosis inducing ability. Notable antitumor efficacies of 7b (5 mg/kg) and 8b (2.5 mg/kg) were observed in the in vivo tumor xenograft experiments, however, lethal toxicities were observed on higher dosages. Our findings indicated that DLC modification is a viable strategy to enhance the anti-OXPHOS and antitumor efficacies of spinosyn derivatives.
- Lai, Qin,Li, Zeng-Xia,Liu, Li-Jun,Liu, Su-You,Luo, Zhi-Yong,Ma, Da-You,Peng, Kun-Jian,Wang, Long-Long
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- A semisynthesis of 3′-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone
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Spinetoram, a mixture of 3′-O-ethyl-5,6-dihydrospinosyn J (XDE-175-J, major component) and 3′-O-ethylspinosyn L (XDE-175-L, minor component), is a novel kind of green and efficient insecticide with a broad range of action against various insects. Nowadays, spinetoram is widely used in agriculture and food storage. This work reports a 7-step semisynthesis of 3′-O-ethyl-5,6-dihydrospinosyn J from spinosyn A aglycone. The C9-OH and C17-OH of the aglycone are successively connected to 3-O-ethyl-2,4-di-O-methylrhamnose and D-forosamine after selective protection and deprotection steps. Then, with 10% Pd/C as catalyst, the 5,6-double bond of the macrolide was selectively reduced to afford 3′-O-ethyl-5,6-dihydrospinosyn J. In addition, the 3-O-ethyl-2,4-di-O-methylrhamnose is synthesized from rhamnose which is available commercially, while the D-forosamine and aglycone are obtained via the hydrolysis of spinosyn A. High yields were obtained in each step, and all intermediates in the synthesis were characterized by 1H NMR, 13C NMR and MS techniques. This study can be helpful for developing an efficient chemical synthesis of spinetoram, and it also offers opportunities to synthesize spinosyn analogues and rhamnose derivatives.
- Zhang, Kai,Liu, Shenglan,Liu, Anjun,Chai, Hongxin,Li, Jiarong,Lamusi
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p. 2603 - 2609
(2018/01/17)
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- Spinosad hapten and preparation method and application thereof
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The invention discloses hapten and a preparation method and application thereof and particularly relates to spinosad hapten and a preparation method and application thereof. The spinosad hapten has the advantages that the chemical structure of spinosad is retained to a maximum degree, -COOH capable of being coupled with protein is introduced through chemical synthesis modification, and the synthesizing method is simple and high in product purity and yield; an antigen system suitable for animal immunization is prepared by using the spinosad hapten as the raw material, an antibody obtained after the animal immunization is good in titer, specificity and affinity, and the antibody can be used for preparing an enzyme linked immunosorbent assay kit; the kit is simple to operate, low in detection cost, efficient, accurate and fast in detection method, capable of simultaneously detecting a large batch of samples and applicable to the field monitoring of spinosad residues in animal-derived food and the screening of a large amount of samples; the spinosad hapten plays an important role in spinosad detection.
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Paragraph 0026
(2017/08/29)
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- Total Synthesis of (-)-Spinosyn A via Carbonylative Macrolactonization
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Spinosyn A (1), a complex natural product featuring a unique 5,6,5,12-fused tetracyclic core structure, is the major component of spinosad, an organic insecticide and an FDA-approved agent used worldwide. Herein, we report an efficient total synthesis of (-)-spinosyn A with 15 steps in the longest linear sequence and 23 steps total from readily available compounds 14 and 23. The synthetic approach features several important catalytic transformations including a chiral amine-catalyzed intramolecular Diels-Alder reaction to afford 22 in excellent diastereoselectivity, a one-step gold-catalyzed propargylic acetate rearrangement to convert 28 to α-iodoenone 31, an unprecedented palladium-catalyzed carbonylative Heck macrolactonization to form the 5,12-fused macrolactone in one step, and a gold-catalyzed Yu glycosylation to install the challenging β-forosamine. This total synthesis is highly convergent and modular, thus offering opportunities to synthesize spinosyn analogues in order to address the emerging cross-resistance problems.
- Bai, Yu,Shen, Xingyu,Li, Yong,Dai, Mingji
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p. 10838 - 10841
(2016/09/12)
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- Total synthesis of (-)-spinosyn A: Examination of structural features that govern the stereoselectivity of the key transannular Diels-Alder reaction
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(Chemical Equation Presented) A study of elements of stereochemical control in transannular Diels-Alder reactions leading to the decahydro-as-indacene core of (-)-spinosyn A is described. Initial studies focused on macrocyclic pentaene 9, which includes C
- Winbush, SusAnn M.,Mergott, Dustin J.,Roush, William R.
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p. 1818 - 1829
(2008/09/18)
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- Spinosyn G: Proof of structure by semisynthesis
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(Chemical Equation Presented) Spinosyn G was isolated in the late 1980s as a minor component from the broth of our potent, fermentation-derived insecticide spinosad. Its structure was then tentatively identified as 5″-epispinosyn A (3) on the basis of 1H and 13C NMR data, but the 4″-epi compound 4 could not be conclusively ruled out with the data available. Described herein are unambiguous syntheses of both 3 and 4, whereby 3 was proved identical to the natural product. Compound 4 was prepared from intact spinosyn A by a novel F-TEDA-promoted oxidative deamination to the 4″-ketone 5, stereoselective reduction to the equatorial alcohol 6, and nitrogen incorporation via the axial azide 7. Compound 3 was obtained by coupling spinosyn A 17-pseudoaglycone (9) with the N-protected dihydropyran 16 derived from methyl L-ossaminide (14). This gave an ~2:1 mixture of anomeric products 17 with the desired equatorial glycoside predominating, which was then converted to 3 by N-deprotection and methylation.
- Graupner, Paul R.,Martynow, Jacek,Anzeveno, Peter B.
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p. 2154 - 2160
(2007/10/03)
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- Total synthesis of spinosyn A. 2. Degradation studies involving the pure factor and its complete reconstitution
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A total synthesis of natural levorotatory spinosyn A (1) has been achieved. The first objective, to confirm the absolute configurational assignment of tricyclic ketone 2 prepared earlier, was accomplished by oxidative degradation of the macrocyclic lactone ring in 1. The route began with the implementation of a four-step one-pot process that resulted in the efficient conversion of 6 into 18. A combination of periodate cleavage and peracid oxidation events then led to 2. In the reconstruction phase, a Pd- catalyzed coupling of a vinylstannane with an acid chloride reestablished the great majority of the structure in an enantiocontrolled manner. Once macrolactonization had been effected, the 2,3,4-tri-O-methylrhamnose unit was introduced first with exceptionally good stereocontrol. The final glycosidation, which involved a 2-mercaptopyrimidine derivative of D- forosamine, was met with an expectedly diminished percentage of the desired β-anomer.
- Paquette, Leo A.,Collado, Iván,Purdie, Mark
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p. 2553 - 2562
(2007/10/03)
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- Conversion of spinosyn A and spinosyn D to their respective 9- and 17-pseudoaglycones and their aglycones
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Forosamine at the 17-position of spinosyns A and D was hydrolyzed under mild acidic conditions to give the corresponding 17-pseudoaglycones. The tri-O-methylrhamnose at the 9-position of the 17-pseudoaglycone of spinosyn A was hydrolyzed under more vigorous acidic conditions to give the aglycone of spinosyn A. However, these conditions led to decomposition of the 17-pseudoaglycone of spinosyn D, presumably due to more facile protonation of the 5,6-double bond to produce a tertiary carbonium ion which undergoes further rearrangements. Spinosyns J and L (3'-O-demethyl spinosyn A and D, respectively) obtained from fermentation of biosynthetically-blocked mutant strains of Saccharopolyspora spinosa, were oxidized to give the corresponding 3'-keto-derivatives and the resultant keto-sugars were then β-eliminated under basic conditions to give the 9-pseudoaglycones of spinosyns A and D respectively. Forosamine at the 17-position of the 9-pseudoaglycone of spinosyn D was then readily hydrolyzed to yield the aglycone of spinosyn D.
- Creemer, Lawrence C.,Kirst, Herbert A.,Paschal, Jonathan W.
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p. 795 - 800
(2007/10/03)
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