133407-52-0

Upstream product

• 133407-51-9 (1S,3S,4S,5R)-4-benzoyloxy-3-bromo-6-oxabicyclo[3.2.1]octan-7-one 
• 158981-04-5 (1R,3S,4S,5R)-4-benzoyloxy-3-bromo-1-O-imidazothiocarbonyl-6-oxabicyclo[3.2.1]octan-7-one 
• 133407-50-8 3,4-O-benzylidene-1,5-quinolactone 
• 216662-59-8 3,4-O-benzylidene-1,5-quinolactone 1-O-(S-methylxanthate) 
• 216662-57-6 (1S,3R,4R,5R)-3,4-O-Benzylidene-1,3,4-trihydroxy-6-oxabicyclo<3.2.1>octan-7-one 

Downstream Products

• 155386-27-9 (1R,2R,4R)-1-[(tert-butyldimethylsilyl)oxy]-4-(2,2-dibromovinyl)-2-methoxycyclohexane 
• 155386-28-0 (1R,2R,4R)-1-[(tert-butyldimethylsilyl)oxy]-4-ethynyl-2-methoxycyclohexane 
• 155386-29-1 (1R,2R,4R)-1-[(tert-butyldimethylsilyl)oxy]-2-methoxy-4-(1-propynyl)cyclohexane 
• 128684-89-9 (1R,3R,4R) methyl 4-hydroxy-3-methoxy-1-cyclohexanecarboxylate 
• 128209-97-2 (1R,3R,4R)-4-[(tert-butyldimethylsilyl)oxy]-3-methoxycyclohexane-1-carbaldehyde 
• 127604-97-1 methyl (1R,3R,4R)-4-[(tert-butyldimethylsilyl)oxy]-3-methoxycyclohexane-1-carboxylate 
• 133407-53-1 Toluene-4-sulfonic acid (1R,3R,4R)-3-methoxy-4-triisopropylsilanyloxy-cyclohexylmethyl ester 
• 133429-54-6 methyl (1R,3R,4R)-4-benzoyloxy-3-methoxycyclohexane-1-carboxylate 
• 133407-54-2 ((1R,2R,4R)-4-Bromomethyl-2-methoxy-cyclohexyloxy)-triisopropyl-silane 
• 109466-73-1 (-)-(1R,2R,4R)-4-hydroxymethyl-2-methoxycyclohexan-1-ol 
• 158981-05-6 methyl (1R,3R,4R)-4-benzoyloxy-3-hydroxycyclohexane-1-carboxylate 

Relevant academic research and scientific papers

Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin

The sector comprising C24-C34 of FK-506 containing five of the stereogenic centers in this macrolide was synthesized from (-)-quinic acid. Aldol coupling of the C24-C34 unit with a methyl ketone representing C20-C23 of FK-506 proceeded with complete Felkin stereoselectivity to afford the C20-C34 portion of the immunosuppressant. A chelate transition state invoking coordination of a lithium enolate with a trityl ether is proposed to explain this stereoselectivity. The strategy adopted for construction of the C26-C34 moiety of FK-506 was extended to the C34-C42 subunit of rapamycin. A Mukaiyama asymmetric anti-aldol coupling was used to set in place the vicinal diol functionality at C27,28 in the C26-C33 segment of this macrolide.

A practical synthesis of the cyclohexyl part of the immunosuppressant FK506

Starting from the benzylidene lactone 3 of D-(-)-quinic acid the cyclohexyl fragment 15 (C-28-C-34 part) of the immunosuppressant FK506 was synthesized. Key steps include homolytic deoxygenation reactions on compounds 4 and 6 as well as a regioselective opening of the benzylidene acetal 5. Opening of the lactone 7 to provide the methyl ester 8 was followed by methylation of the hydroxy group to give 9. Further steps provided the aldehyde 12 which was elongated to the alkyne 15. This sequence provides 15 in gram quantities.

Studies directed towards the synthesis of immunosuppressive agent FK-506: Synthesis of the entire top-half

An efficient approach has been developed to construct the entire TOP-HALF of FK-506 involving Grignard reaction of a C-29 bromide with a C-27 methylketo fragment.