193073-38-0

Upstream product

• 193073-48-2 (S)-N-(tert-butoxycarbonyl)-N-methyl-(S)-(4-fluoro-3-nitro)phenylalanine methyl ester 
• 459-57-4 4-fluorobenzaldehyde 
• 74-88-4 methyl iodide 
• 24424-99-5 di-tert-butyl dicarbonate 
• 193073-45-9 methyl 2-((tert-butoxycarbonyl)amino)-3-(4-fluoro-3-nitrophenyl)propanoate 
• 178744-39-3 L-4-fluoro-3-nitrophenylalanine methyl ester 
• 15017-52-4 4-(bromomethyl)-1-fluoro-2-nitrobenzene 
• 42564-51-2 4-fluoro-3-nitrobenzaldehyde 
• 20274-69-5 (4-fluoro-3-nitrophenyl)methanol 

Downstream Products

• 193073-96-0 [(2S)-2-(tert-butoxycarbonylmethylamino)-3-(4-fluoro-3-nitrophenyl)propionylamino]-(R)-(4-methoxyphenyl)methyl ester 
• 193073-99-3 [3-(4-fluoro-3-nitrophenyl)-(2S)-2-methylaminopropionylamino]-(R)-(4-methoxyphenyl)acetic acid methyl ester 
• 193074-02-1 [2-{(R)-[tert-butoxycarbonylamino-(3,5-dichloro-4-methoxyphenyl)acetyl]methylamino}-(3S)-3-(4-fluoro-3-nitrophenyl)propionylamino]-(R)-(4-methoxyphenyl)acetic acid methyl ester 
• 249757-20-8 (S)-[(S)-2-{[(R)-2-Amino-2-(3,5-dichloro-4-methoxy-phenyl)-acetyl]-methyl-amino}-3-(4-fluoro-3-nitro-phenyl)-propionylamino]-(4-methoxy-phenyl)-acetic acid methyl ester 
• 249757-14-0 [2-({(R)-(3,5-dichloro-4-methoxyphenyl)-[2-(3-hydroxyphenyl)acetylamino]acetyl}methylamino)-(3S)-3-(4-fluoro-3-nitrophenyl)propionylamino]-(S)-(4-methoxyphenyl)acetic acid methyl ester 
• 193074-05-4 [2-{(R)-[amino-(3,5-dichloro-4-methoxyphenyl)acetyl]methylamino}-(3S)-3-(4-fluoro-3-nitrophenyl)propionylamino]-(R)-(4-methoxyphenyl)acetic acid methyl ester 
• 249757-19-5 (R)-[(S)-2-{[(S)-2-Amino-2-(3,5-dichloro-4-methoxy-phenyl)-acetyl]-methyl-amino}-3-(4-fluoro-3-nitro-phenyl)-propionylamino]-(4-methoxy-phenyl)-acetic acid methyl ester 
• 193074-12-3 [2-({(S)-(3,5-dichloro-4-methoxyphenyl)-[2-(3-hydroxyphenyl)acetylamino]acetyl}methylamino)-(3S)-3-(4-fluoro-3-nitrophenyl)propionylamino]-(R)-(4-methoxyphenyl)acetic acid methyl ester 
• 193074-08-7 [2-({(R)-(3,5-dichloro-4-methoxyphenyl)-[2-(3-hydroxyphenyl)acetylamino]acetyl}methylamino)-(3S)-3-(4-fluoro-3-nitrophenyl)propionylamino]-(R)-(4-methoxyphenyl)acetic acid methyl ester 
• 1195785-28-4 C₂₄H₂₈FN₃O₈ 

Relevant academic research and scientific papers

Total synthesis of complestatin: Development of a Pd(0)-mediated indole annulation for macrocyclization

Full details of the initial development and continued examination of a powerful intramolecular palladium(0)-mediated indole annulation for macrocyclization closure of the strained 16-membered biaryl ring system found in complestatin (1, chloropeptin II) and the definition of factors impacting its intrinsic atropodiastereoselectivity are described. Its examination and use in an alternative, second-generation total synthesis of complestatin are detailed in which the order of the macrocyclization reactions was reversed from our first-generation total synthesis. In this approach and with the ABCD biaryl ether ring system in place, the key Larock cyclization was conducted with substrate 36 (containing four phenols, five secondary amides, one carbamate, and four labile aryl chlorides) and provided the product 37 (56%) exclusively as a single atropisomer (>20:1, detection limits) possessing the natural (R)-configuration. In this instance, the complexity of the substrate and the reverse macrocyclization order did not diminish the atropodiastereoselectivity; rather, it provided an improvement over the 4:1 selectivity that was observed with the analogous substrate used to provide the isolated DEF ring system in our first-generation approach. Just as significant, the atroposelectivity represents a complete reversal of the diasteroselectivity observed with analogous macrocyclizations conducted using a Suzuki biaryl coupling.

Total synthesis of chloropeptin II (complestatin) and chloropeptin I

(Chemical Equation Presented) The first total synthesis of chloropeptin II (1, complestatin) is disclosed. Key elements of the approach include the use of an intramolecular Larock indole synthesis for the initial macrocyclization, adopting conditions that

Synthetic studies towards the synthesis of western and eastern chloropeptin I, II subunits

The western subunit (16-membered ring) was synthesized by the intramolecular SNAr reaction while the first 16-membered ring compound was obtained as a model of the eastern subunit via an intramolecular Ni0 mediated coupling reaction.

Synthesis of a model of chloropeptins I, II western subunit by the intramolecular S(N)Ar based methodology

Formation of a biaryl ether bond between the termini of a tetrapeptide containing a highly racemization prone amino acid by the intramolecular SNAr reaction afforded two diastereomeric 16-membered macrocycles along with their respective atropoisomers. The (R,S,R) and its atropoisomer constituted model of chloropeptins I, II, western part.