The intramolecular asymmetric Pauson-Khand cyclization as a novel and general stereoselective route to benzindene prostacyclins: synthesis of UT-15 (treprostinil)

A general and novel solution to the synthesis of biologically important stable analogues of prostacyclin PGI(2), namely benzindene prostacyclins, has been achieved via the stereoselective intramolecular Pauson-Khand cyclization (PKC). This work illustrates for the first time the synthetic utility and reliability of the asymmetric PKC route for synthesis and subsequent manufacture of a complex drug substance on a multikilogram scale. The synthetic route surmounts issues of individual step stereoselectivity and scalability. The key step in the synthesis involves efficient stereoselection effected in the PKC of a benzoenyne under the agency of the benzylic OTBDMS group, which serves as a temporary stereodirecting group that is conveniently removed via benzylic hydrogenolysis concomitantly with the catalytic hydrogenation of the enone PKC product. Thus the benzylic chiral center dictates the subsequent stereochemistry of the stereogenic centers at three carbon atoms (C(3a), C(9a), and C(1)).     

Stereoselective synthesis of aminocyclitol moieties of trehazolin and trehalostatin via enyne metathesis protocol

Stereoselective and efficient synthesis of respective aminocyclitol moieties 1a and 2a of trehazolin and trehalostatin as hexaacetates 1b and 2b using ring-closing enyne metathesis as the key reaction is described.     

Azidocarbonyl-substituted cubanoureas

Despite the angular strain associated with the assembly of small rings, 1,2-diisocyanatocubane reacts with trimethylsilyl azide under mild conditions to form a hexacyclic ring assembly that contains an imidazolidone ring fused to one edge of cubane. This compound was identified as an azidocarbonyl-substituted cubanourea by means of X-ray crystal structure analysis of the nitro-derivative, the energetic compound N-azidocarbonyl-N¹-nitrocubanourea.     

Cost reduction approaches for fermentable sugar production from sugarcane bagasse and its impact on techno-economics and the environment

Cellulose - In an enzymatically driven lignocellulosic biorefinery, pretreatment and hydrolysis modules are the two most significant cost contributors for obtaining high gravity sugar solutions....     

A constant factor approximation algorithm for the fault-tolerant facility location problem

We consider a generalization of the classical facility location problem, where we require the solution to be fault-tolerant. In this generalization, every demand point j must be served by r_j facilities instead of just one. The facilities other than the closest one are “backup” facilities for that demand, and any such facility will be used only if all closer facilities (or the links to them) fail. Hence, for any demand point, we can assign nonincreasing weights to the routing costs to farther facilities. The cost of assignment for demand j is the weighted linear combination of the assignment costs to its r_j closest open facilities. We wish to minimize the sum of the cost of opening the facilities and the assignment cost of each demand j. We obtain a factor 4 approximation to this problem through the application of various rounding techniques to the linear relaxation of an integer program formulation. We further improve the approximation ratio to 3.16 using randomization and to 2.41 using greedy local-search type techniques.     

Total Synthesis of Leiocarpin C and (+)‐Goniodiol via an Olefin Cross‐Metathesis Protocol

A stereoselective total synthesis of leiocarpin C ( 2 ) and (+)‐Goniodiol ( 1 ) by applying olefin cross‐metathesis and substrate directed dihydroxylation as the key steps is reported (Scheme 3).