Second-generation synthesis systems

Second-generation synthesis systems are characterised by using a data-driven approach to generating the verbal content of the signal. 

We now turn to unit selection synthesis which is the dominant synthesis technique in text-to-speech today. Unit selection is the natural extension of second generation concatenative systems, and deals with the issues of how to manage large numbers of units, how to extend prosody beyond just FO and timing control, and how to alleviate the distortions caused by signal processing. 

In 2007, the same group reported a second-generation catalytic system using 10mol% of Cul/phenanthroline and 3mol% Pd(acac)2 for the synthesis of unsymmetrical biaryls... 

Another facet of the second generation HAL system is a new methodology [31] for high-level controller specification and synthesis which is partly based on the concepts of Harel s statecharts [32]. The long term goal is to create a high-level synthesis environment which supports both DSP style q>plications as well high-level controllor applications (such as protocols). 

Deoxypancratistatin Keck, 1998 In 1995, Keck reported his first synthesis of 7-deoxypancratistatin (298) with a radical cyclization as key step [178]. A few years later, a second-generation synthesis of this important Amaryllidaceae constituent was reported [173]. The route, outlined in Schemes 12.50 and 12.51, started from inexpensive and commercially available L-gulonolactone (289) and featured a highly efficient radical cyclization cascade, which established two ring systems of the natural product. This radical cyclization protocol is quite unique in the preparation of Amaryllidaceae alkaloids and constitutes an interesting alternative to commonly employed coupling protocols. 

Alkali-promoted Ru-based catalysts are expected to become the second generation NHs synthesis catalysts [1]. In 1992 the 600 ton/day Ocelot Ammonia Plant started to produce NH3 with promoted Ru catalysts supported on carbon based on the Kellogg Advanced Ammonia Process (KAAP) [2]. The Ru-based catalysts permit milder operating conditions compared with the magnetite-based systems, such as low synthesis pressure (70 -105 bars compared with 150 - 300 bars) and lower synthesis temperatures, while maintaining higher conversion than a conventional system [3]. 

Initial efforts in the ring-dosing metathesis approach were attempted with substrates 34 and 35. However, after employing a variety of catalysts and experimental conditions, no cydized systems (36 or 37) were obtained. Other substrates were prepared to further probe this unexpected failure however, no observable reaction was realized. Model systems later suggested that die dense functionality between C3 and C8 was the culprit for lack of macrocycle formation. Eventually a second generation Cl2-03 RCM (not shown here) approach was developed [26] which yielded mixtures of C12-C13 Z/E isomers that were used in early SAR studies. [26b] However, since the separation of products was so difficult, we did not seriously pursue this route for total synthesis. 

Scheme 2.6 provides an overall view of our strategy towards solving this problem. As depicted, our late generation synthesis embraces three key discoveries that were crucial to its success. We anticipated that the difficult Cl-Cll polypropionate domain could be assembled through a double stereodifferentiating aldol condensation of the C5-C6 Z-metalloenolate system B and chiral aldehyde C. Two potentially serious problems are apparent upon examination of this strategy. First was the condition that the aldol reaction must afford the requisite syn connectivity between the emerging stereocenters at C6-C7 (by uk addition) concomitant with the necessary anti relationship relative to the resident chirality at C8 (by Ik diastereoface addition). Secondly, it would be necessary to steer the required aldol condensation to C6 in preference to the more readily enolizable center at C2. 

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