Diels-Alder reaction-aromatization approach toward functionalized ring C allocolchicinoids. Enantioselective total synthesis of (-)-7S-allocolchicine

Allocolchicinoids are analogues of the important antimitotic compound (-)-colchicine 1. A strategy is reported for the synthesis of ring C functionalized allocolchicinoids, which is based on a Diels-Alder reaction-aromatization sequence. This route is complementary to the previously disclosed benzannulation approach involving Fischer carbene complexes and alkynes. Dienes 12 and 14 incorporate the natural substitution pattern on ring A and undergo Diels-Alder reactions with various dienophiles. Subsequent aromatization affords the set of differently functionalized ring C allocolchicinoids 15-19, 23, and 25, with high regioselectively and in moderate to good yields. An intramolecular Diels-Alder reaction-aromatization sequence allows for access to allocolchicinoids with reversed regiochemical introduction of ring C substituents. The equilibria of the atropisomers of 15 and 19 are studied in three NMR solvents. Reactions of the dienes 12 and 14 with DMAD lead to the corresponding cycloadducts, but the subsequent aromatization is complicated. A regioselective Diels-Alder reaction-aromatization sequence is utilized as the key step in the first stereoselective total synthesis of (-)-allocolchicine 2. Asymmetric introduction of hydroxy group at C7 is achieved by the enantioselective reduction of ketone 29. The correct stereochemistry is then established by Mitsunobu inversion reaction using Zn(N(3))(2)-2Py.     

The pyrrole approach toward the synthesis of fully functionalized cup-shaped molecules

[reaction: see text] A novel method for the synthesis of new highly functionalized cyclotrimers is described. The method consists of an original synthesis of beta-dibromosubstituted pyrroles, metalation, cycloaddition, and cyclotrimerization. The sequence is highly compatible with common functional groups and allows the construction of cup-shaped molecules functionalized both at the upper and bottom rim. This feature makes the newly formed structures useful scaffolds for the development of supramolecular receptors.     

Convergent synthesis of the HIJKLM ring system of ciguatoxin CTX3C

The HIJKLM ring system of ciguatoxin CTX3C was synthesized in a convergent manner. The key steps were a conjugate addition/alkylation sequence, spiroacetalization, intramolecular allylation, ring-closing metathesis, and hydrogenation to form the 36-α-methyl substituent.     

Convergent synthesis of the A-E ring segment of ciguatoxin CTX3C

A convergent synthesis of the A-E ring segment of ciguatoxin CTX3C was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

Synthetic studies toward the zoanthamine alkaloids: synthesis of the fully functionalized BC ring motif

A synthetic approach toward lactone 20, representing the fully functionalized BC ring motif of the zoanthamine alkaloids, has been developed and is presented herein. The challenging C9 quaternary center of 20 was installed by a Wilkinson hydrogenation of enone 17 followed by construction of an α-bromo acetal and intramolecular cyclization exclusively from the α face of the BC ring system.     

Convergent synthesis of functionalized fluoroallylamines by the Julia-Kocienski reaction

The synthesis of β-fluoroallylamines is reported from aminofluorobenzothiazolylsulfones. These open a new route for a short synthesis of vinylic fluoride containing highly functionalized amino residues.     

Synthesis of the fully functionalized ABCDE ring moiety of ciguatoxin

A fully functionalized ABCDE ring moiety of ciguatoxin (CTX), the major causative agent of ciguatera poisoning, was synthesized for the first time. The present strategy involves the efficient installation of the C5-dihydroxybutenyl substituent and construction of the tetrahydrooxepin E ring using a novel alpha-chlorosulfide synthon. [structure: see text]     

Convergent synthesis of the FGHI ring segment of yessotoxin

A convergent synthesis of the FGHI ring segment of yessotoxin was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

Convergent synthesis of the ABCDE ring fragment of ciguatoxins

Synthesis of the ABCDE ring fragment of ciguatoxins has been achieved in a highly stereocontrolled and convergent manner via the B-alkyl Suzuki-Miyaura coupling-based approach.     

Convergent synthesis of a fully lipidated glycosylphosphatidylinositol anchor of Plasmodium falciparum

A highly convergent strategy for the synthesis of fully lipidated GPI anchors of malarial origin is reported. This strategy utilized three orthogonal protecting groups, which can be chemoselectively deprotected and functionalized in the late stage of the synthesis. Rapid access to the target GPIs in a highly efficient manner in sufficient quantities for the biological studies has been achieved.     

Convergent synthesis of the F-K ring segment of brevetoxin B

A convergent synthesis of the F-K ring segment of brevetoxin B has been achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

Convergent synthesis of a polyfunctionalized fullerene by regioselective five-fold addition of a functionalized organocopper reagent to C60

[reaction: see text] A method for one-step preparation of polyfunctionalized fullerene derivatives by regioselective penta-addition of an organocopper reagent is described. A functionalized aryl iodide is first converted to the corresponding Grignard reagent and then to a copper reagent and finally is allowed to react with C(60). The method allows introduction of five functional groups to the C(60) skeleton in a convergent manner. The shuttlecock-like molecules crystallize into a columnar packing structure.     

Chiron approach to fully functionalized cyclohexane frame of (+)-Resiniferatoxin

The commercially available (−)-Shikimic acid is used to construct the fully functionalised cyclohexane frame (C-ring) of (+)-Resiniferatoxin. The key reactions involve stereo-selective epoxide opening with trimethylaluminium and vinyl Grignard reaction.     

Convergent synthesis of the A-F ring segment of yessotoxin and adriatoxin

A convergent synthesis of the A-F ring segment of yessotoxin and adriatoxin was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

Synthesis of sesbanimide: An approach for the synthesis of ring C

A simple method for the construction of C-ring of sesbanimide utilizing the condensation of 2-benzyloxymethylcrotyl bromide with an aldehyde in the presence of zinc as the key step is described.     

Preparation of fully substituted anilines for the synthesis of functionalized indoles

A wide range of highly functionalized indoles were prepared by the successive magnesiation of readily available o-alkynyl protected anilines using TMPMgCl.LiCl or LDA, followed by a KH-mediated cyclization reaction.     

Three-component synthesis of functionalized five-membered ring lactones under Barbier-like conditions

Five-membered ring lactones have been synthesized using a straightforward three-component reaction among in situ-generated arylzinc reagents, dimethyl itaconate and aromatic aldehydes. This Barbier-like procedure, which is characterized by its simplicity, allows the concise synthesis of a range of highly functionalized 4,5-substituted γ-butyrolactones.     

Convergent synthesis of the FGHI ring system of yessotoxin: stereoselective construction of the G ring

A convergent synthetic route to the FGHI ring system of yessotoxin, a marine ladder polyether, has been developed. The synthesis features convergent coupling of the diol and the aldehyde to form α-cyano ethers via acetal formation followed by ring closing metathesis and reductive etherification to construct the oxocane ring G and tetrahydropyran ring H, respectively. The β-methyl group on the G ring was stereoselectively introduced by alkylation of the corresponding ketone.     

Convergent synthesis of a fully phosphorylated GPI anchor of the CD52 antigen

A fully phosphorylated GPI anchor (1) of the CD52 antigen was synthesized by a highly convergent strategy. After a trimannose and a phospholipidated pseudodisaccharide were prepared separately, they were coupled together to form the GPI core, which was then phosphorylated to introduce two phosphoethanolamine moieties in one step to afford CD52 GPI in its fully protected form. Finally, global deprotection of the product resulted in 1.