Refernces
10.1021/ol100233t
The study presents the first Br?nsted acid-catalyzed asymmetric Mukaiyama aldol reaction using silyl enol ethers of ketones as nucleophiles with aldehydes. The primary chemicals used were various aldehydes, silyl enol ethers of ketones, and chiral N-trifluorothiophosphoramide catalysts (specifically 1-3). The purpose of these chemicals was to achieve the aldol reaction, which resulted in the formation of new carbon-carbon bonds and up to two new stereogenic centers in the products. The study aimed to improve upon previous methods by using less reactive silyl enol ethers of ketones and to explore the mechanism behind the reaction, revealing that the actual catalyst may switch from the silylated Br?nsted acid to the Br?nsted acid itself depending on the reaction temperature. This finding could potentially expand the scope of enantioselective Mukaiyama aldol reactions.
10.1021/ol015988w
The study investigates the use of vinyl imidates in intramolecular Diels?Alder reactions to efficiently synthesize cis-fused perhydroisoquinoline ring systems, exemplified by the preparation of an intermediate, isoquinoline 2, which can be transformed into reserpine. The researchers employed N-acylvinylimidates as the 2π electron component in these reactions, leveraging their potential for stereochemical control. The process began with the Stille coupling of vinylstannane 66 and methyl (3E)-bromopropenoate (7) to produce diene 8, which was then converted to diene 5 via kinetic deconjugation and saponification. The Diels-Alder precursor was formed by coupling diene 5 with 1-aza-2-ethoxy-1,3-butadiene (9), mediated by 2-chloro-1-methylpyridinium iodide, yielding N-acylvinylimidate 4. Cycloaddition of this compound resulted in the formation of cycloadducts, with the major product, 3, having a cis-ring fusion. Further steps included reduction, carbamate formation, hydroboration, oxidation, and acetylation to complete the synthesis of perhydroisoquinoline 2. This work highlights the utility of vinyl imidates in constructing complex isoquinoline ring systems with significant stereochemical complexity.
10.1021/acs.jnatprod.7b00359
The research focuses on the synthesis and evaluation of dolastatin 10 analogues, which are of significant interest in cancer research due to their potent in vitro activity and potential use as payloads in antibody drug conjugates (ADCs). The study aims to modify the P2 subunit of the dolastatin 10 core scaffold by introducing heteroatoms to the P2 side chain, resulting in compounds that maintain potent in vitro activity. The most active compounds were found to contain azides in the P2 unit and required a phenylalanine-derived P5 subunit. The researchers synthesized a series of auristatins, which are derivatives of dolastatin 10, using various amino acids and chemical modifications, including amines, azides, oxygens, and thiols. Key chemicals used in the synthesis process included Fmoc-protected amino acids, CMPI (2-chloro-1-methylpyridinium iodide), HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate), TFA (trifluoroacetic acid), and other reagents for specific coupling and deprotection steps. The conclusions of the research indicated that the P2 side chain modifications could be active in vitro, but these modified compounds followed a different activity trend than valine-based P2 compounds, and the presence of an ester or amide at the P5 position was crucial for the activity of these molecules in vitro.
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