DKP Total Syntheses

To date, only a few examples of the total syntheses of the large family of (T)DKPs are known. In particular, the introduction of a sulfur bridge to obtain TDKPs remains a challenge (407). After the first total synthesis in 1981 of a TDKP, gUotoxin, by Kishi et al. (408), it took almost 30 years until additional compounds of this type were synthesized, in and after 2009 (see Sect. 10.2.2). Selected examples of (T)DKP total syntheses will be presented in the next two sections (10.2.1 and 10.2.2). 

After NBS oxidation ( 619), Fmoc-deprotection led to dihydrospirotry-prostatin B (620). A phenylselenylation reaction yielded 621 and a small amount of 622 among many side products. Compound 621 could be converted to spirotry-prostatin B (622) by consecutive Boc-protection, elimination, and Boc-deprotection in good yields. This synthesis route is not an efficient strategy for the preparation of the natural product 622, but gives a versatile method for the rapid synthesis of its analogs. 

In 2000, two further diketopiperazine derivatives, the anti-microtubule compounds phenylahistin (633a) and aurantiamine (633b), were synthesized by Hayashi et al. (413). Their synthesis started with the aldol reaction of ethyl iso- 

633a R = benzyl pbenylahistin 633h R = isopropyl aurantiamine 

Compound 636 was converted to 638 under Mitsunohu conditions. Reduction upon heating led to the cyclization product 639. Coupling with a (R)-phenylalanine derivative yielded tetrapeptide 640, which was deprotected to give free diol 641. Diacid 642 was obtained after two consecutive oxidation steps with Dess-Martin periodinane and NaC102. Fmoc-deprotection, DCC-mediated cyclization (— 643) and benzyl deprotection furnished diketopiperazine enf-WIN 64821 (644). 

---