Synthesis of Steroid−Biaryl Ether Hybrid Macrocycles with High Skeletal and Side Chain Variability by Multiple Multicomponent Macrocyclization Including Bifunctional Building Blocks

2006 ◽  
Vol 71 (20) ◽  
pp. 7521-7526 ◽  
Author(s):  
Ludger A. Wessjohann ◽  
Daniel G. Rivera ◽  
Francisco Coll
Keyword(s):  
Building Blocks ◽  
Side Chain ◽  
Biaryl Ether

Zur Totalsynthese des Human-Big-Gastrins I und seines 32-Leucin-Analogons (Vorläufige Mitteilung) / Total Synthesis of Human Big Gastrin I and the 32-Leucine Analogue (Preliminary Communication)

1977 ◽  
Vol 32 (7-8) ◽  
pp. 495-506 ◽  
Author(s):  
E. Wünsch ◽  
G. Wendlberger ◽  
A. Hallett ◽  
E. Jaeger ◽  
S. Knof ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Building Blocks ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Protecting Groups ◽  
Side Chain ◽  
Tertiary Alcohols ◽  
Synthetic Product ◽  
Preliminary Communication ◽  
Final Purification

A new total synthesis of the tetratriacontapeptide amide corresponding to the proposed primary structure of human big gastrin I is described. The synthetic route was based on the preparation of six suitably protected fragments, related to sequence 28 - 34, 23 - 27, 21 - 22, 15-20, 9 - 14, and 1 - 8, to be used as building blocks for the total synthesis. The protecting groups were selected according to the Schwyzer-Wünsch strategy of maximum side chain protection based on tertiary alcohols, also for the imidazol function of histidine. Subsequent assembly of the six fragments by three different pathways using the highly efficient Wünsch-Weygand condensation procedure to ensure minimum racemization, followed by deprotection of the synthetic products via exposure to trifluoroacetic acid and final purification by ion-exchange chromatography on DEAE-Sephadex A-25 and partition chromatography on Sephadex G-25, led to human big gastrin I, homogeneous within the limits of the analytical methods used. The biological activity of the synthetic product proved to be 50 percent higher than that of human little gastrin I. The 32-leucine analogue of human big gastrin I was prepared in the same way.

scholarly journals P450 monooxygenase ComJ catalyses side chain phenolic cross-coupling during complestatin biosynthesis

RSC Advances ◽  
2017 ◽  
Vol 7 (56) ◽  
pp. 35376-35384 ◽  
Author(s):  
Aurelio Mollo ◽  
A. Nikolai von Krusenstiern ◽  
Joshua A. Bulos ◽  
Veronika Ulrich ◽  
Karin S. Åkerfeldt ◽  
...  
Keyword(s):  
High Efficiency ◽  
Bond Formation ◽  
Cross Coupling ◽  
Side Chain ◽  
P450 Monooxygenase ◽  
Peptide Substrates ◽  
Ether Bond ◽  
Biaryl Ether

P450 monooxygenase enzyme ComJ catalyzed biaryl ether bond formation with high efficiency and low stereoselectivity on selected complestatin-like peptide substrates.

Enantioselective synthesis of structurally intricate and complementary polyoxygenated building blocks of Spongistatin 1 (Altohyrtin A)

2009 ◽  
Vol 74 (5) ◽  
pp. 651-769 ◽  
Author(s):  
Alain Braun ◽  
Il Hwan Cho ◽  
Stephane Ciblat ◽  
Dean Clyne ◽  
Pat Forgione ◽  
...  
Keyword(s):  
Suzuki Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Side Chain ◽  
Spongistatin 1 ◽  
Enantiomerically Pure ◽  
Altohyrtin A ◽  
Stereogenic Centers ◽  
Complex Building ◽  
Synthetic Effort

Enantioselective approaches to the construction of four complex building blocks of the structurally intricate marine macrolide known as spongistatin 1 are presented. The first phase of the synthetic effort relies on a practical approach to a desymmetrized, enantiomerically pure spiroketal ring system incorporating rings A and B. Concurrently, the C17–C28 subunit, which houses one-fifth of the stereogenic centers of the target in the form of rings C and D, was assembled via a composite of stereocontrolled aldol condensations. Once arrival at the entire C1–C28 sector had been realized, routes were devised to provide two additional highly functionalized sectors consisting of C29–C44 and C38–C51. A series of subsequent transformations including cyclization of the E ring and hydroboration to afford the B-alkyl intermediate for the key Suzuki coupling to append the side chain took advantage of efficient stereocontrol. Ultimately, complete assembly and functionalization of the western EF sector of spongistatin was thwarted by an inoperative Suzuki coupling step intended to join the side chain to the C29–C44 sector, and later because of complications due to protecting groups, which precluded the complete elaboration of the late stage C29–C51 intermediate.

scholarly journals FlhA Undergoes Cyclic Open-close Domain Motions During Flagellar Protein Export in Salmonella

2021 ◽  
Author(s):  
Tohru Minamino ◽  
Yumi Inoue ◽  
Miki Kinoshita ◽  
Akio Kitao ◽  
Keiichi Namba
Keyword(s):  
Closed Form ◽  
Protein Transport ◽  
Building Blocks ◽  
Protein Export ◽  
Side Chain ◽  
Transport Activity ◽  
Flagellar Assembly ◽  
Flagellar Protein ◽  
Domain Motions

Abstract The flagellar type III secretion system (fT3SS) transports flagellar building blocks from the cytoplasm to the distal end of the growing flagellar structure. The C-terminal cytoplasmic domain of FlhA (FlhAC) serves as a docking platform for flagellar chaperones in complex with their cognate substrates and ensures the strict order of protein export for efficient flagellar assembly. FlhAC adopts open and closed conformations, and the chaperones bind to the open form, allowing the fT3SS to transport the substrates to the cell exterior. To clarify the role of the closed form in flagellar protein export, we isolated pseudorevertants from the flhA(G368C/K549C) mutant, in which the closed conformation is stabilized to inhibit the protein transport activity of the fT3SS. Each of M365I, R370S, A446E and P550S substitutions in FlhAC identified in the pseudorevertants affected hydrophobic side-chain interaction networks in the closed FlhAC structure, thereby restoring the protein transport activity to a considerable degree. We propose that a cyclic open-close domain motion of FlhAC is required for rapid and efficient flagellar protein export where a structural transition from the open to the closed form induces the dissociation of empty chaperones from FlhAC.

scholarly journals A versatile strategy for the synthesis of sequence-defined peptoids with side-chain and backbone diversity via amino acid building blocks

2019 ◽  
Vol 10 (5) ◽  
pp. 1531-1538 ◽  
Author(s):  
Shixue Wang ◽  
Yue Tao ◽  
Jianqun Wang ◽  
Youhua Tao ◽  
Xianhong Wang
Keyword(s):  
Amino Acid ◽  
De Novo ◽  
Building Blocks ◽  
Side Chain ◽  
Design And Synthesis

De novo design and synthesis of sequence-defined peptoids via amino acid building blocks is reported.

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