120205-50-7Relevant academic research and scientific papers
Synthesis of both syn and anti diastereoisomers of Boc-dolaproine from (S)-proline through DKR using ruthenium-catalyzed hydrogenation: A dramatic role of N-protecting groups
Mordant, Céline,Reymond, Sébastien,Ratovelomanana-Vidal, Virginie,Genêt, Jean-Pierre
, p. 9715 - 9723 (2004)
The natural (2R,3R)-Boc-dolaproine and its unnatural (2S,3S) diastereoisomer were synthesized involving as key transformation the Ru(II)-promoted hydrogenation of the β-keto-α-methyl ester derived from (S)-N-Boc-proline. Interestingly, the asymmetric hydrogenation of this β-keto ester N-protected as an amine hydrochloride salt, provided the corresponding anti (2S,3R)- and (2R,3S)-β-hydroxy-α-methyl esters with significant level of selectivities through dynamic kinetic resolution. Graphical Abstract.
Stereoselective synthesis of the dolastatin units by organotrifluoroborates additions to α-amino aldehydes
Cella, Rodrigo,Venturoso, Raphael C.,Stefani, Hélio A.
, p. 16 - 19 (2008)
Dolastatin units were synthesized from the 1,2-addition reactions of potassium allyl or crotyltrifluoroborate salts to aldehyde derivatives from natural amino acids. The reactions were carried out in presence of a phase-transfer catalyst in a biphasic medium at room temperature and excellent yields (>89-93%) and stereoselective (>90:10 to 98:2) were obtained. The dolastatin units 8 and 14a-b were obtained after three steps in good overall yields (50-62%).
An easy and stereoselective synthesis of N-Boc-dolaproine via the Baylis-Hillman reaction
Almeida, Wanda P.,Coelho, Fernando
, p. 937 - 940 (2003)
In this communication we report a stereoselective total synthesis of N-Boc-dolaproine (Dap), an amino acid residue of the antineoplastic pentapeptide Dolastatin 10. Our strategy is based on a Baylis-Hillman reaction between N-Boc-prolinal and methyl acrylate, followed by a diastereoselective double bond hydrogenation and hydrolysis of the ester function.
NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG
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, (2021/05/14)
PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
EFFICIENT PREPARATION OF DOLASTATIN AND AURISTATIN ANALOGS THROUGH A COMMON INTERMEDIATE
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, (2021/09/17)
Methods for making a dolastatin, auristatin or related compounds comprising the steps of providing a universal dolastatin core of Formula (I) reacting the C-terminal carboxylic acid group with an amine (A) to form an amide bond and reacting the N-terminal amine with a carboxylic acid (CA) to form an amide bond, wherein the steps can be performed in either order. Also provided are an isolated salt of the universal dolastatin core for use in preparation of dolastatins, auristatins and related compounds. Also provided are a number of intermediates and process steps which are useful for the preparation of high purity dolastatin core and high purity dolastatin and auristatin compounds.
CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP
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, (2020/05/19)
Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.
Synthesis method of N-Boc-Dolaproine and synthesis method of Boc-Dap DCHA
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, (2020/07/21)
The invention discloses a synthesis method of N-Boc-Dolaproine and a synthesis method of Boc-Dap DCHA. The synthesis method comprises the following steps: 1) subjecting a compound shown in the specification and a compound shown in the specification to a Reformatsky reaction under the activation of zinc powder to synthesize a compound shown in the specification, with X being Cl or Br or I, and R being alkane or olefin; 2) subjecting the compound shown in the specification to methylation to obtain a compound shown in the specification; 3) carrying out a hydrolysis reaction on the compound shownin the specification so as to obtain N-Boc-Dolaproine. By applying the technical scheme of the invention, the yield of each step of reaction is relatively good, the intermediates are easy to purify, the process route used by the method is relatively short, the material price is relatively low, the synthesis process is simple to operate, the production cost is further reduced, and the methods can be applied to industrial production.
CONJUGATION OF A CYTOTOXIC DRUG WITH BIS-LINKAGE
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, (2020/01/08)
What provided is the conjugation of cytotoxic to a cell-binding molecule with a bis-linker(dual-linker) as shown in Formula (I). It provides bis-linkage methods of making a conjugate of a cytotoxic drug molecule to a cell-binding agent in a specific manner. It also relates to application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.
CONJUGATION LINKERS, CELL BINDING MOLECULE-DRUG CONJUGATES CONTAINING THE LIKERS, METHODS OF MAKING AND USES SUCH CONJUGATES WITH THE LINKERS
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, (2018/05/27)
The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.
Method for synthesizing aplysiatoxin Dap fragment with high stereoselectivity
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Paragraph 0082-0083, (2017/11/29)
The invention discloses a synthesis method for preparation of an aplysiatoxin Dap fragment. The method comprises steps as follows: (L)-N-tert-butoxycarboryl-prolinal (II) and (R)-4-benzyl-3-propionyloxazolidin-2-one (III) are taken as raw materials for preparation of an intermediate (I); after the intermediate (I) is subjected to hydrolysis, an intermediate (IV) is obtained; the intermediate (IV) is subjected to methylation, and the aplysiatoxin Dap fragment with high stereoselectivity is obtained; or the prepared intermediate (I) can also be subjected to methylation firstly, an intermediate (V) is generated and subjected to hydrolysis, and the aplysiatoxin Dap fragment with high stereoselectivity is obtained. The preparation method is low in cost and simple and convenient to operate, and the stereoselectivity is high.
