Synthetic route to pactamycin and pactamycin analogs
Methods and intermediates useful for making compounds of Formula (I) are described, including a general method of making an alpha, beta-diamino ketone by reacting an imine with a 2-amino-substituted 1,3-dicarbonyl in a Mannich addition reaction to produce said alpha,beta-diamino ketone.
1. A compound of Formula IX:
wherein:
R 8 is H, hydroxy, silyloxy, acyloxy, or alkoxy; and
R 9 is —N(R c R d ), —OR c , or —SR c , where R c and R d are each independently selected alkyl, aryl, or heteroaryl, or R c and R d together form an alkylene bridge; and
X is a protecting group.
2. A method of making a compound of Formula IX:
wherein:
R 8 is H, hydroxy, silyloxy, acyloxy, or alkoxy; and
R 9 is —N(R c R d ), —OR c , or —SR c , where R c and R d are each independently selected alkyl, aryl, or heteroaryl, or R c and R d together form an alkylene bridge; and
X is a protecting group;
said method comprising condensing a compound of Formula X:
in an aldol condensation reaction to produce said compound of Formula IX.
3. A compound of Formula X:
wherein:
R 8 is H, hydroxy, silyloxy, acyloxy, or alkoxy; and
R 9 is —N(R c R d ), —OR c , or —SR c , where R c and R d are each independently selected alkyl, aryl, or heteroaryl, or R c and R d together form an alkylene bridge; and
X is a protecting group.