Total Synthesis of 1‐Hydroxytaxinine

Abstract

1-Hydroxytaxinine (1)isacytotoxic taxane diterpenoid. Its central eight-membered B-ring possesses four oxygenfunctionalizedc enters (C1, C2, C9, and C10) and two quaternary carbon centers (C8 and C15), and is fused with six-membered A-and C-rings.The densely functionalizedand intricately fused structure of 1 makes it ah ighly challenging synthetic target. Reported here is an efficient radical-based strategy for assembling 1 from A-and C-ring fragments.T he A-ring bearing an a-alkoxyacyl telluride moiety underwent intermolecular coupling with the C-ring fragment by aE t 3 B/ O 2 -promoted decarbonylative radical formation. After construction of the C8-quaternary stereocenter,apinacol coupling reaction using alow-valent titanium reagent formed the B-ring with stereoselective installation of the C1,C2-diol. Subsequent manipulations at the A-and C-rings furnished 1 in 26 total steps.

Recent advances in the synthesis of taxoids: 2015-2020

“…Inoue's group reported the first total synthesis of 1-hydroxytaxinine (61, Scheme 11). 49 Their retrosynthetic analysis required the introduction of oxygen functionality at C5, C7 and C13 of a nearly complete carbon skeleton (62). They envisioned generation of the C1-C2 bond in the B ring by a pinacol coupling of the ketoaldehyde 63.…”

“…Conjugate addition of methyl Grignard in the presence of CuI to 70 proceeded predominantly on theface (Scheme 13). 49 Reduction of the resultant -cyano cyclohexanone, mesylation of the secondary alcohol and elimination with DBU gave the corresponding -unsaturated nitrile 71 as an inseparable mixture of diastereomers at C8. Reduction of the nitrile, followed by aqueous acidic work-up (for hydrolysis of the imine and cyclic ketal) led to a separable mixture of the desired stereoisomer (-)-63 and 72.…”

Construction of C-C bonds via photoreductive coupling of ketones and aldehydes in the metal-organic-framework MFM-300(Cr)

“…Aldehydes and ketones are among the most valuable organic compounds that can be obtained from renewable resources, such as biomass, in large scale. Reductive coupling of aldehydes and ketones offers a promising route to the synthesis of 1,2-diols, which are important structural motifs in a broad range of natural products 3 , pharmaceuticals 4 , protease inhibitor 5 , peptidomimetics 6 and polymers 7 , and are widely used as chiral ligands and auxiliaries in organic reactions 8 . However, this is a very challenging photochemical process owing to the highly negative reduction potential of carbonyl compounds, particularly for ketones [e.g., acetophenone: E 1/2red = −1.79 V vs. normalised hydrogen electrode (NHE) 9 ] and to date, success has only been achieved in exceptional cases 9 – 14 .…”

Recent Advances of Cinnamic Acids in Organic Synthesis

“…Cinnamic acids ( α,β ‐unsaturated carboxylic acids) are reactive molecules because of the carboxylic acid and the polarized alkenyl moiety. The updated methodologies in the last decade showed their significances in total synthesis of natural products, such as Brevipolide M, Teixobactin, Tetragocarbone A, (+)‐Absouline, Citridone A, (+)‐Decursivine, 1‐Hydroxytaxinine, (+)‐Crassalactones B and C, (−)‐Jorumycin, (+)‐Indatraline, (−)‐( 1R,7aS )‐Absouline, Englerin A, B, Orientalol E, F, and Oxyphyllol . Besides, cinnamic acids are known for their biological efficacy, which include anticancer, antioxidant, antimicrobial as well as applications in diabetes, tuberculosis, malaria and cardiovascular diseases…”