Total synthesis of an antitumor agent, mucocin, based on the "chiron approach".
The total synthesis of a powerful antitumor acetogenin, mucocin (1), was achieved through a palladium-catalyzed cross-coupling reaction of the THP-THF fragment 2 and a terminal butenolide 3. The key process for construction of the fragment 2 was chelation-controlled addition of ethynylmagnesium chloride to disilyl aldehyde 23a and condensation of the alkyllithium prepared therefrom with THP aldehyde 4 in the presence of CeCl(3). Synthesis of the lactone 3 relied on a novel approach by taking advantage of a radical cyclization of acyclic selenocarbonate 6. The three building blocks 4, 5a, and 6 were prepared stereoselectivly from D-galactose (7), 2,5-anhydro-D-mannitol (8), and L-rhamnose (9), respectively. A new and efficient method for desymmetrization of the C(2)-symmetrical compound 8 is also described.
Takahashi
Shunya
S
RIKEN, The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan. shunyat@riken.go.jp
Nakata
Tadashi
T
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D007536:Isomerism; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007783:Lactones; D011714:Pyrans; C413144:mucocin