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Fmoc/tBu Protection Strategy

The Nalpha-Fmoc group is removed by base (typically 20% piperidine in DMF) via E1cb elimination, while tBu-type side-chain groups and the linker are removed by TFA at the end, making the two axes orthogonal in mechanism rather than merely graded in acid strength. It is the default modern strategy because no HF handling is required.

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The Nalpha-Fmoc group is removed by base (typically 20% piperidine in DMF) via E1cb elimination, while tBu-type side-chain groups and the linker are removed by TFA at the end, making the two axes orthogonal in mechanism rather than merely graded in acid strength. It is the default modern strategy because no HF handling is required.

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