A new commercial-scale alternative manufacturing process to produce a complementary source of artemisinin to supplement the plant-derived supply is described by conversion of biosynthetic artemisinic acid into semisynthetic artemisinin using diastereoselective hydrogenation and photooxidation as pivotal steps. This process was accepted by Prequalification of Medicines Programme (PQP) in 2013 as a first source of nonplant-derived-artemisinin in industrial scale from Sanofi production facility in Garessio, Italy.

The coupling of building blocks 15 and 36e in the presence of MgBr(2).OEt(2) at 0 degrees C proceeds with an exo stereoselectivity (3.2:1) considerably more advantageous for the acquisition of carbinol 37e than in the absence of the additive (exo/endo = 1:5.7). The pivotal transformation that sets all of the relevant stereocenters of the cis-octalin 55 is the oxyanionic-accelerated [3,3]-sigmatropic rearrangement of 37e. A salient feature is the structurally enforced adoption of a boatlike transition state that serves to properly set four vicinal methine hydrogens in an all-cis arrangement. The ensuing conversion of 55 into iodo sulfone 62 has permitted X-ray crystallographic confirmation of all absolute stereochemical assignments since the isopropyl substituent was initially installed enantioselectively via the Evans oxazolidinone protocol. No intramolecular anionic cyclization of 62 to generate the tricyclic framework was seen. This absence of reactivity is attributed to conformational factors that inhibit attainment of the proper S(N)2 reaction trajectory.

We study a particular class of moving average processes that possess a property called localizability. This means that, at any given point, they admit a "tangent process," in a suitable sense. We give general conditions on the kernel g defining the moving average which ensures that the process is localizable and we characterize the nature of the associated tangent processes. Examples include the reverse Ornstein-Uhlenbeck process and the multistable reverse OrnsteinUhlenbeck process. In the latter case, the tangent process is, at each time t , a Lévy stable motion with stability index possibly varying with t . We also consider the problem of path synthesis, for which we give both theoretical results and numerical simulations.

The study of non-stationary processes whose local form has controlled properties is a fruitful and important area of research, both in theory and applications. In [9], a particular way of constructing such processes was investigated, leading in particular to multifractional multistable processes, which were built using sums over Poisson processes. We present here a different construction of these processes, based on the Ferguson -Klass -LePage series representation of stable processes. We consider various particular cases of interest, including multistable Lévy motion, multistable reverse Ornstein-Uhlenbeck process, log-fractional multistable motion and linear multistable multifractional motion. We also show that the processes defined here have the same finite dimensional distributions as the corresponding processes constructed in [9]. Finally, we display numerical experiments showing graphs of synthesized paths of such processes.