First-generation synthesis

The second category of coal Hquefaction iavolves those processes which first generate synthesis gas, a mixture of CO and by steam gasification of coal... 

Synthesis of the Cl-Cll domain of the epothilones at first appeared quite forbidding because of the need to gain facile control over the stereocenters at C3, C6, C7, and C8. Indeed, this region has been the scene of many variations in strategy and synthetic design. [12] Our first generation synthesis of the Cl-Cll acyl domain, al-... 

A comparison of the amount of waste produced per kilogram of sitagliptin manufactured by the two processes demonstrates the improved efficiency of the new route (Figure 5.6). Overall, the new route reduces the total waste output of the process by approximately 80%. This will result in over 220000 kg less waste per 1000 kg of sitagliptin produced. While the first-generation synthesis produced over 60 L of aqueous waste per kg of 1, the new route produces no aqueous waste only 2 liters of water per kg of sitagliptin is now required for its preparation. 

The first-generation synthesis of levetiracetam (3), as shown in Scheme 14.9 [29], starts with benzoyl protection and oxidation of (S)-aminobutanol (32), which gives rise to the corresponding N-benzoyl protected (S)-aminobutyric acid (33). After N-benzoyl amidation and deprotection, (S)-aminobutyramide (34) is obtained. Chemoselective butyrolactam ring formation using the intermediate 34 and 4-chlorobutyryl chloride finally affords levetiracetam (3). 

The second-generation synthesis of (S,S)-TaDiAS 1 is summarized in Scheme 6.1 [16], This process requires only common and inexpensive reagents under operationally simple reaction conditions. When using the first-generation synthesis (a five-step process from diethyl tartrate) [4a] or the second-generation synthesis (a four-step process from tartaric acid), a variety of catalysts with versatility on the acetal moieties (R1 and R2) and aromatic parts (Ar) were synthesized (over 100 derivatives) [18]. A large-scale reaction (>20g) can also be performed with the same efficiency. 

Z E = 49 1). At this stage, the (Z)-diene unit was introduced utilizing the Yamamoto olefmation protocol to give 43 [115]. A further five steps were then required to complete Smith s first-generation synthesis of (-)-discodermolide (ent-1), in 2.2% overall yield over 28 steps in the longest linear sequence based on the C1-C8 aldehyde 28. 

In the initial study we completed the total synthesis of (+)goniofufurone (3) (eq. 14) (30), the key component of styryl lactones which showed anti-tumor activities. As a first generation synthesis, we felt that even though it uses water as a solvent, it was still too long. Presently, we are developing a second generation synthesis in which only three steps are involved (Scheme 2). With this method, a variety of structurally related natural products, such as papulacandin D (9) andchactiacandin... 

First-generation synthesis systems have specific rules for each type of emotion. 

Merck used a first-generation synthesis of sitagliptin to prepare over 200 pounds for clinical trials. With modifications, this synthesis could have been a viable manufacturing process, but it required eight... 

SCHEME 10.12 First-generation synthesis of LY2140023 46 through Bucherer-Bergs hydantoin. 

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