A unified strategy for the total syntheses of eribulin and a macrolactam analogue of halichondrin b

A compound of the formula:

• wherein:
• X1, X2, and X3 are each independently a covalent bond, alkanediyl(C≤8), substituted alkanediyl(C≤8), NRa, O, and S;
• wherein:
• Ra is hydrogen, alkyl(C≤8), or substituted alkyl(C≤8);
• Y1, Y2, and Y3 are each independently CRbRb′, ORb″, S, or NRc, wherein
• Rb, Rb′, and Rc are each independently hydrogen, alkylz(C≤8), or substituted alkyl(C≤8);
• and
• Rb″ is absent, hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), substituted acyl(C≤8),
• x, y, and z are each independently 1, 2, or 3;
• R1 is hydrogen, alkyl(C≤8), or substituted alkyl(C≤8);
• R2 and R3 are each independently alkyl(C≤12), alkenyl(C≤12), alkynyl(C≤12), alkoxy(C≤12), alkylamino(C≤12), dialkylamino(C≤12), acyl(C≤12), acyloxy(C≤12), amido(C≤12), or a substituted version thereof;
• or either two R3 groups and R2 and R3 are taken together to form one or more cycloalkanediyl(C≤18), arenediyl(C≤18), heteroarenediyl(C≤18), heterocycloalkanediyl(C≤18), or a substituted version thereof;
• or a group of the formula:
• —AR3′, wherein A is alkanediyl(C≤8) or substituted alkanediyl(C≤8);
• and R3′ is NRdC(X4)NRd′Rd″, wherein X1 is O or NRe, wherein Re is hydrogen, alkyl(C≤8), or substituted alkyl(C≤8), and Rd, Rd′, and Rd″ are each independently hydrogen, alkyl(C≤8), or substituted alkyl(C≤8);
• and
• n is 1 or 2;
• provided that for each n, then each R3 is separately selected;
• provided that the compound is not eribulin;
• or a pharmaceutically acceptable salt thereof.