Total synthesis

About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.

Total synthesis of bryostatin 7 via C-C bond-forming hydrogenation.

Abstract: The marine macrolide bryostatin 7 is prepared in 20 steps (longest linear sequence) and 36 total steps with five C–C bonds formed using hydrogenative methods. This approach represents the most concise synthesis of any bryostatin reported, to date.

Total synthesis of the thiopeptide antibiotic amythiamicin D.

Abstract: The thiopeptide (or thiostrepton) antibiotics are a class of sulfur containing highly modified cyclic peptides with interesting biological properties, including reported activity against MRSA and malaria. Described herein is the total synthesis of the thiopeptide natural product amythiamicin D, which utilizes a biosynthesis-inspired hetero-Diels−Alder route to the pyridine core of the antibiotic as a key step. Preliminary studies using a range of serine-derived 1-ethoxy-2-azadienes established that hetero-Diels−Alder reaction with N-acetylenamines proceeded efficiently under microwave irradiation to give 2,3,6-trisubstituted pyridines. The thiazole building blocks of the antibiotic were obtained by either classical Hantzsch reactions or by dirhodium(II)-catalyzed chemoselective carbene N−H insertion followed by thionation, and were combined to give the bis-thiazole that forms the left-hand fragment of the antibiotic. The key Diels−Alder reaction of a tris-thiazolyl azadiene with benzyl 2-(1-acetylaminoeth...

Total synthesis and structural investigations of didemnins A, B, and C

Abstract: Didemnins A, B, and C were efficiently prepared in a stereocontrolled manner, producing the common macrocycle and, in a separate step, introducing the substituents on the amino group of L-threonine as optically pure units. We envisaged that disconnections between L-leucine and the HIP group (2S,4S) and between L-threonine and isostatine (3S,4R,5S) would afford two units: a HIP-isostatine unit (I) and a tetrapeptide unit (II)

A Concise Total Synthesis of Dactylol via Ring Closing Metathesis

Abstract: A straightforward total synthesis of the cyclooctenoid sesquiterpene dactylol (1) and of 3a-epi-dactylol (13) has been achieved in six synthetic operations. The unusual rearranged bicyclo[6.3.0]undecane isoprenoid skeleton of these target molecules has been formed via an initial three-component coupling triggered by 1,4-addition of a methylcopper reagent (MeLi, CuI, Bu(3)P) to cyclopentenone, followed by trapping of the enolate formed with 2,2-dimethyl-4-pentenal as the electrophile. The aldol 8 thus obtained was elaborated into the trans-disubstituted cyclopentanone derivative 10 which reacted with a methallylcerium reagent to afford a mixture of the tertiary alcohols 11a and 12a. Separation and O-silylation of these diastereoisomers, ring-closing metathesis (RCM) of the resulting dienes 11b and 12b to form the cyclooctene ring using Schrocks molybdenum carbene 5 as a precatalyst, and a final deprotection afforded the title compound and its epimer in excellent yields. This approach clearly surpasses previous ones in terms of efficiency, flexibility, accessibility of the substrates, number of steps, atom economy, and overall yield.