Total Synthesis of Apoptolidin: Part 1. Retrosynthetic Analysis and Construction of Building Blocks

Total Synthesis and Stereochemical Assignment of (−)-Ushikulide A

“…Varying the Lewis acid (SnCl 4 , CH 2 Cl 2 , Entry 2) led to only a negligible increase in diastereoselectivity. Fortunately, ample precedent suggested that this problem could be overcome by reagent-control 18. In our case, using either antipode of Brown’s19 ( Z )-crotyl-B(Ipc) 2 reagent led to excellent control of stereochemistry for the preparation of 19a or 19b in >20:1 d.r.…”

Stereoselective Formation of 2‐Deoxyglycosidic Bonds in Biologically Active Natural Products

“…71 Sulfur and selenium species were also employed as other temporary participating groups at C2, which could be easily removed using either a tin hydride-based reagent or Raney Ni and H 2 . 72 This method was successfully applied to the total synthesis of apoptolidin, 73,74 which was discussed in detail in section 3.2. In addition, desulfurization with Raney Ni and H 2 afforded the corresponding 2-deoxyglycoside 123 (Scheme 38.30).…”

Metal‐Catalyzed Cross‐Coupling Reactions of Organoboron Compounds with Organic Halides

“…Disiamylborane (HB(Sia) 2 ), dicyclohexylborane, and 9-BBN are very mild and selective hydroboration reagents by which to obtain 1-alkenylboranes, which can be directly used for subsequent cross-coupling reactions. The addition of catecholborane (HBcat) or dihaloborane (HBCl 2 · SMe 2 , HBBr 2 · SMe 2 ) to alkynes, followed by hydrolysis with water, is a common method for the synthesis of air-stable 1-alkenylborinic acids 8 [14]. Hydroboration of alkynes with catecholborane is slow in tetrahydrofuran (THF), with the reaction occurring at room temperature in the presence of a catalytic amount of 9-BBN or dicyclohexylborane (ca.…”

“…The utility of the benzannulation-crosscoupling sequence has been demonstrated in the synthesis of a dimeric carbazole, bis-N-dimethylbismurrayaquinone A. The reaction between lithium carbenoids and diboron (13) or silylboron (14) [87] is particularly attractive for preparing a new class of boron compounds such as 1,1-bisborylalkenes and 1-silyl-1-borylalkenes (64) [87][88][89]. The addition of 14 to a solution of alkenylidene carbenoid at -110 hC forms an ate-complex (63), which is then followed by intramolecular S N 2 substitution with complete inversion of the configuration at the a-carbon.…”

“…Since a variety of 1-alkenylboron compounds, including (E)-and (Z)-isomers, are now available, the alkenyl-alkenyl coupling reaction has been used for the synthesis of various biologically active natural products, including: a macrolide antibiotic, rutamycin B [313]; (5Z,8Z,10E,12R,14Z)-12-hydroxy-5,8,10,14-icosatetraenoic acid [(12R)-HETE] [314], an antiproliferative agent; (þ)-curacin A [298], an aglycone of chlorothricin; (-)-chlorothricolide [315], a member of a small family of C 15 lupinine alkaloids; (þ)-aloperine [316], restrictinols that exhibit antifungal activity [317]; marine alkaloids, (-)-lepadins A, B, and C [318]; a highly unsaturated 20-membered macrocyclic system having four carbohydrate units, apoptolidin [14]; and cytotoxic substances FR 182877 and clinic acid [319]. The synthesis of polyene natural products via metal-catalyzed protocol has recently been reviewed [320].…”