551-11-1Relevant articles and documents
NEW PROSTAGLANDIN (PGF) DERIVATIVES FROM THE SOFT CORAL LOBOPHYTON DEPRESSUM
Carmely, S.,Kashman, Y.,Loya, Y.,Benayahu, Y.
, p. 875 - 878 (1980)
Four PGF derivatives (15S)-PGF2α-11-acetate methyl ester (1a), the 18-acetoxy derivative of compound 1a (2a) as well as their two corresponding free carboxylic acids (1b and 2b) were isolated from a soft-coral and their structure elucidated, mainly on basis of their spectral data.
Concise, scalable and enantioselective total synthesis of prostaglandins
Zhang, Fuhao,Zeng, Jingwen,Gao, Mohan,Wang, Linzhou,Chen, Gen-Qiang,Lu, Yixin,Zhang, Xumu
, p. 692 - 697 (2021/06/01)
Prostaglandins are among the most important natural isolates owing to their broad range of bioactivities and unique structures. However, current methods for the synthesis of prostaglandins suffer from low yields and lengthy steps. Here, we report a practicability-oriented synthetic strategy for the enantioselective and divergent synthesis of prostaglandins. In this approach, the multiply substituted five-membered rings in prostaglandins were constructed via the key enyne cycloisomerization with excellent selectivity (>20:1 d.r., 98% e.e.). The crucial chiral centre on the scaffold of the prostaglandins was installed using the asymmetric hydrogenation method (up to 98% yield and 98% e.e.). From our versatile common intermediates, a series of prostaglandins and related drugs could be produced in two steps, and fluprostenol could be prepared on a 20-gram scale. [Figure not available: see fulltext.]
Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer–Villiger Oxidation
Zhu, Kejie,Hu, Sha,Liu, Minjie,Peng, Haihui,Chen, Fen-Er
, p. 9923 - 9927 (2019/05/16)
A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer–Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey′s route. Furthermore, the reactivity and enantioselectivity of B-V oxidation of racemic bicyclic cyclobutanones were evaluated and 90–99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone-containing natural products to promote drug discovery.
Total synthesis of PGF2α and 6,15-diketo-PGF1α and formal synthesis of 6-keto-PGF1α via three-component coupling
Kim, Taehyeong,Lee, Sung Il,Kim, Sejin,Shim, Su Yong,Ryu, Do Hyun
, (2019/09/17)
The asymmetric total synthesis of PGF2α and 6,15-diketo-PGF1α and formal synthesis of 6-keto-PGF1α from a common key intermediate are described. The key intermediate, which has a chiral cyclopentane backbone possessing suitable functional groups with required stereochemistry for both side chains, was prepared from (R)-4-silyloxy-2-cyclopentenone through a three-component coupling reaction. The Wittig reaction, Nozaki-Hiyama-Kishi (NHK) coupling and cross metathesis completed the synthesis of PGF2α, 6,15-diketo-PGF1α and 6-keto-PGF1α.
METHOD OF MAKING A CROSS METATHESIS PRODUCT
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Paragraph 00122; 00123; 00124; 00125, (2019/02/06)
Method of making a cross metathesis product, the method comprising at least step (X) or step (Y): (X) reacting in a cross metathesis reaction a first compound comprising a terminal olefinic group with a second compound comprising a terminal olefinic group, wherein the first and the second compound may be identical or may be different from one another; or (Y) reacting in a ring-closing metathesis reaction two terminal olefinic groups which are comprised in a third compound; wherein the reacting in step (X) or step (Y) is performed in the presence of a ruthenium carbene complex comprising a [Ru=C]-moiety and an internal olefin.
Of the trometamol prostaglandin F2 α synthesis method (by machine translation)
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, (2017/08/30)
The invention discloses a of the trometamol prostaglandin F2 α synthesis method, as the compound (-) - Corey lactone diol as raw materials, through the oxidation reaction to obtain lactone aldehyde, lactone aldehydechain after the weidiWeidi Greecehuo Naer reaction with - the lower side of the splicing an olefin, the olefin double-carbonyl after reduction to obtain the alcohol, with puncture ylide - wittich reaction the upper side of the obtained prostaglandin F2 α, then the prostaglandin F2 α of the trometamol after crystallization by dissolving of the trometamol prostaglandin F2 α. The synthesis method, without noble metal catalyst, there is little side reaction, high yield, low cost, less pollution, is suitable for industrial production. (by machine translation)
In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive Catalytic Olefin Metathesis. the Concept, Methodological Implications, and Applications to Synthesis of Biologically Active Compounds
Xu, Chaofan,Shen, Xiao,Hoveyda, Amir H.
, p. 10919 - 10928 (2017/08/15)
In situ methylene capping is introduced as a practical and broadly applicable strategy that can expand the scope of catalyst-controlled stereoselective olefin metathesis considerably. By incorporation of commercially available Z-butene together with robust and readily accessible Ru-based dithiolate catalysts developed in these laboratories, a large variety of transformations can be made to proceed with terminal alkenes, without the need for a priori synthesis of a stereochemically defined disubstituted olefin. Reactions thus proceed with significantly higher efficiency and Z selectivity as compared to when other Ru-, Mo-, or W-based complexes are utilized. Cross-metathesis with olefins that contain a carboxylic acid, an aldehyde, an allylic alcohol, an aryl olefin, an α substituent, or amino acid residues was carried out to generate the desired products in 47-88% yield and 90:10 to >98:2 Z:E selectivity. Transformations were equally efficient and stereoselective with a ～70:30 Z-:E-butene mixture, which is a byproduct of crude oil cracking. The in situ methylene capping strategy was used with the same Ru catechothiolate complex (no catalyst modification necessary) to perform ring-closing metathesis reactions, generating 14- to 21-membered ring macrocyclic alkenes in 40-70% yield and 96:4-98:2 Z:E selectivity; here too, reactions were more efficient and Z-selective than when the other catalyst classes are employed. The utility of the approach is highlighted by applications to efficient and stereoselective syntheses of several biologically active molecules. This includes a platelet aggregate inhibitor and two members of the prostaglandin family of compounds by catalytic cross-metathesis reactions, and a strained 14-membered ring stapled peptide by means of macrocyclic ring-closing metathesis. The approach presented herein is likely to have a notable effect on broadening the scope of olefin metathesis, as the stability of methylidene complexes is a generally debilitating issue with all types of catalyst systems. Illustrative examples of kinetically controlled E-selective cross-metathesis and macrocyclic ring-closing reactions, where E-butene serves as the methylene capping agent, are provided.
Decarboxylative alkenylation
Edwards, Jacob T.,Merchant, Rohan R.,McClymont, Kyle S.,Knouse, Kyle W.,Qin, Tian,Malins, Lara R.,Vokits, Benjamin,Shaw, Scott A.,Bao, Deng-Hui,Wei, Fu-Liang,Zhou, Ting,Eastgate, Martin D.,Baran, Phil S.
, p. 213 - 218 (2017/05/19)
Olefin chemistry, through pericyclic reactions, polymerizations, oxidations, or reductions, has an essential role in the manipulation of organic matter. Despite its importance, olefin synthesis still relies largely on chemistry introduced more than three decades ago, with metathesis being the most recent addition. Here we describe a simple method of accessing olefins with any substitution pattern or geometry from one of the most ubiquitous and variegated building blocks of chemistry: alkyl carboxylic acids. The activating principles used in amide-bond synthesis can therefore be used, with nickel- or iron-based catalysis, to extract carbon dioxide from a carboxylic acid and economically replace it with an organozinc-derived olefin on a molar scale. We prepare more than 60 olefins across a range of substrate classes, and the ability to simplify retrosynthetic analysis is exemplified with the preparation of 16 different natural products across 10 different families.
Synthesis of Alfaprostol and PGF2α through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step
Baars, Hannah,Classen, Moritz J.,Aggarwal, Varinder K.
, p. 6008 - 6011 (2017/11/10)
The veterinary drug Alfaprostol and prostaglandin PGF2α have been synthesized in just nine steps. The strategy involved the conjugate addition of an alkyne to a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest synthesis reported to date. For PGF2α, this approach improved our previous route by making the 1,4-addition and ozonolysis more operationally simple.
Rh(I)-Catalyzed 1,4-Conjugate Addition of Alkenylboronic Acids to a Cyclopentenone Useful for the Synthesis of Prostaglandins
Syu, Jin-Fong,Wang, Yun-Ting,Liu, Kung-Cheng,Wu, Ping-Yu,Henschke, Julian P.,Wu, Hsyueh-Liang
, p. 10832 - 10844 (2016/11/29)
An efficient and trans-diastereoselective Rh(I)-catalyzed 1,4-conjugate addition reaction of alkenylboronic acids and a homochiral (R)-4-silyloxycyclopentenone useful for the synthesis of derivatives of prostaglandins E and F is described for the first time. The reaction functions under mild conditions and is particularly rapid (≤6 h) under low power (50 W) microwave irradiation at 30 °C in MeOH in the presence of a catalytic amount of KOH. Under these conditions, 3 mol % of [RhCl(COD)]2 is typically required to produce high yields. The method also functions without microwave irradiation at 3 °C in the presence of a stoichiometric amount of KOH. Under these conditions, only 1.5 mol % of [RhCl(COD)]2 is needed, but the reaction is considerably slower. The method accepts a range of aryl- and alkyl-substituted alkenylboronic acids, and its utility has been demonstrated by the synthesis of PGF2α (dinoprost) and tafluprost.
