90721-41-8

Upstream product

• 1011-27-4 3,5-dimethoxy-4-methylbenzaldehyde 
• 72922-63-5 3-Hydroxy-5-methoxy-4-methyl-benzonitril 

Downstream Products

• 685869-30-1 [(R)-2-Hydroxy-1-(3-{3-methoxy-5-[(S)-2-(2-methoxy-ethoxymethoxy)-1-(2,2,2-trifluoro-acetylamino)-ethyl]-2-methyl-phenoxy}-4-nitro-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 685869-32-3 [(R)-2-Hydroxy-1-(4-hydroxy-3-{3-methoxy-5-[(S)-2-(2-methoxy-ethoxymethoxy)-1-(2,2,2-trifluoro-acetylamino)-ethyl]-2-methyl-phenoxy}-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 685869-31-2 [(R)-1-(4-Amino-3-{3-methoxy-5-[(S)-2-(2-methoxy-ethoxymethoxy)-1-(2,2,2-trifluoro-acetylamino)-ethyl]-2-methyl-phenoxy}-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester 
• 685869-28-7 (1S)-N-benzyloxycarbonyl-1-(3-(benzyloxy)-5-methoxy-4-methylphenyl)-2-((2-methoxyethoxy)methoxy)ethylamine 
• 685869-29-8 (1S)-N-trifluoroacetyl-1-(3-hydroxy-5-methoxy-4-methylphenyl)-2-((2-methoxyethoxy)methoxy)ethylamine 
• 301530-16-5 3-benzyloxy-5-methoxy-4-methylstyrene 

Relevant academic research and scientific papers

Total Synthesis of the Ristocetin Aglycon

The first total synthesis of the ristocetin aglycon is described employing a modular and highly convergent strategy. An effective 12-step (12% overall) synthesis of the ABCD ring system 3 from its amino acid subunits sequentially features an intramolecular aromatic nucleophilic substitution reaction for formation of the diaryl ether and closure of the 16-membered CD ring system (65%), a respectively diastereoselective (3:1, 86%) Suzuki coupling for installation of the AB biaryl linkage on which the atropisomer stereochemistry can be further thermally adjusted, and an effective macrolactamization (51%) for closure of the 12-membered AB ring system. A similarly effective 13-step (14% overall) synthesis of the 14-membered EFG ring system 4 was implemented employing a room-temperature intermolecular SNAr reaction of an o-fluoronitroaromatic for formation of the FG diaryl ether (69%) and a key macrolactamization (92%) with formation of the amide linking residues 1 and 2. The two key fragments 3 and 4 were coupled, and the remaining 16-membered DE ring system was closed via diaryl ether formation to provide the ristocetin tetracyclic ring system (15 steps, 8% overall) enlisting an unusually facile (25 °C, 8 h, DMF, ≥95%) and diastereoselective (≥15:1) aromatic nucleophilic substitution reaction that benefits from substrate preorganization.